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The series follows eight to ten crab fishing boats and their crews throughout two of the dangerous crab fishing seasons, the October king crab (frequently called "red crab" or "red gold" by crew members) season and the January opilio crab ("orange crab", "orange gold", or, as Northwestern crew member Matt Bradley dubbed it, "Norwegian money") season. The show emphasizes the very real danger to the crew on the decks of these boats, situations are just as dangerous for the Discovery Channel camera crews filming them as they are for any other member of the fleet. Each episode has a focus on a story or situation that occurs on one or more boats, with side stories on the backgrounds and particular activities of one or two crew members, in particular the "greenhorns" (inexperienced crew members) on several boats. The fleet's captains are featured prominently throughout the episodes, highlighting their camaraderie with their fellow captains and relationships with their crew, as well as their competitive nature against the other boats in the fleet regarding the hunt for crab throughout the fishing grounds. Common themes woven throughout the overarching storyline of the particular fishing season include friendly rivalries between the captains (particularly Jonathan Hillstrand of the Time Bandit and Phil Harris of the Cornelia Marie), the familial ties throughout the fleet (the Hansen brothers, who own the Northwestern; Phil Harris and his two sons on the Cornelia Marie; brothers Johnathan and Andy Hillstrand of the Time Bandit), the stresses of life on the Bering Sea, and the high burnout rate among greenhorns.

Because Alaskan crab fishing is one of the most dangerous jobs in the world, the U.S. Coast Guard rescue squads stationed at Integrated Support Command Kodiak (Kodiak, Alaska) and their outpost on St. Paul Island, near the northern end of the crab fishing grounds, are frequently shown doing their own dangerous work: rescuing crab boat crew members who fall victim to the harsh conditions on the Bering Sea. The USCG rescue squad was featured prominently during the episodes surrounding the loss of F/V Big Valley in January 2005 and the loss of F/V Ocean Challenger in October 2006. The Discovery Channel keeps a camera crew stationed with the Coast Guard during the filming of the show.

The show has no on-camera host; instead, narrators provide commentary and verbally connect the storylines as the show shifts from one crab boat to another, through a mock-up radar transition screen that shows the boats in relation to each other and to the two ends of the fishing grounds, St. Paul Island to the north and Dutch Harbor to the south. Discovery Channel voice artist Mike Rowe, who narrates the U.S. airings of the series, was originally supposed to be the on-camera host as well and had appeared in taped footage as himself during the first season of shooting; as filming of the first season was nearing completion, Discovery greenlighted production on another Rowe project, Dirty Jobs, under the condition that Rowe choose only one show upon which to appear in person. As Rowe relates the story, Discovery told him that the two shows would be airing back-to-back on the same night, thus, "'we can't have you telling us stories about six dead fishermen on camera and making a fart joke with your arm in a cow's ass.'"[3] Most of the footage Rowe shot during the first season became part of the first season's "Behind the Scenes" episode and Rowe later hosted the After the Catch specials in which the captains had a roundtable discussion of their experiences.

In North America, the series is narrated by Mike Rowe, while Bill Petrie, reading from a slightly altered script, provides a regionally familiar accent for the English speaking viewers of the show in Europe. The show takes a unique approach to censoring profanities spoken by the crews, using sound effects such as a ship's horn or a burst of radio static in addition to traditional bleeping.

The Behind the Scenes special provided insight on how the program is produced. A two-person TV crew lives on each boat profiled. They use handheld Sony HVR-Z1U HDV cameras to shoot most of the series (one on the main deck, one in the wheelhouse). Additional footage is provided by four stationary cameras that are permanently mounted around the ship and are constantly recording. Shots from vantage points outside the boat are accomplished through a variety of methods, including the use of a helicopter (for footage near the harbor) and a cameraman on a chase boat (in season 1, the main chase boat was the Time Bandit). The crew also makes use of underwater cameras, including one attached to a crab pot for a "crab's eye view" of the pot being retrieved in season 2, one mounted in the main crab tank on the Northwestern beginning in season 2, and one mounted to a submersible watercraft beginning in season 3.

Because of a lack of space on the boats, the crews do not have a sound recordist. Audio is recorded using wireless microphones worn by the fishermen and shotgun microphones attached to the cameras.

Although the equipment is carefully waterproofed, the cameras are routinely damaged by saltwater corrosion, ice, and accidents. By the end of each production cycle, most of the fifty cameras (which cost, on average, $7,000 each) are no longer usable.

Filming episodes of Deadliest Catch is a dangerous occupation for the camera crews onboard the boats. In the early seasons, when many of the camera crews had little to no experience on crab boats, they frequently ran into dangers not normally encountered when filming a documentary. Northwestern captain Sig Hansen told talk show host Jimmy Kimmel that he saved a cameraman's life during the first season, screaming at him to get out of the way just seconds before a 900-pound crab pot swinging from a crane crossed the space where the cameraman had been standing and filming the storm surge[4]. In another incident, showcased on the behind the scenes special, an inattentive cameraman ended up having his leg fall through an open hatch on the deck of one of the boats when he unwittingly stepped into the hole, suffering three broken ribs (and, according to the cameraman himself, having to buy beer for the entire crew as per tradition on crab boats).

Some shots that would be difficult to capture with cameras are computer-generated imagery (CGI):

• CGI was used in the first two seasons to demonstrate how the severely cold water of the Bering Sea causes men without survival suits to drown within minutes, showing the decrease in blood flow and the gradual failure of vital organs.
• In the second episode of the first season, CGI was used to show how a crab trap works.
• In the early episodes of season 2, CGI was used to show how the overloaded deck of the Big Valley caused it to sink.
• The playful sea lions tearing open the Northwestern's crab pot buoys at the start the Opilio crab season in season 3 were computer generated.
• In episode 4 of season 4, CGI was used to show how the falling cable of the picking hook of the Time Bandit would have killed greenhorn Shea Long had it failed a few seconds later when a pot was attached to it.

Sig Hansen, captain of the Northwestern, and Larry Hendricks, retired captain of the Sea Star who now runs a boat repair facility in Dutch Harbor, serve as technical advisors to the series' producers.