The crew of a naval destroyer is forced to confront the reality of a new existence when a pandemic kills off most of the earth's population.

Season Two begins with a cure for the Red Virus and the goal to save the human race. Navy Captain Tom Chandler and his crew return to the States unsure of what they will find. As the crew seeks to find survivors and their families, they encounter a new, emerging enemy who’s vying for control and may hinder the mass production of the cure.

The crew of the Nathan James is shifting their attention to Asia after President Michener hears rumblings that the Chinese leader has been hoarding the "Scott cure" instead of distributing it to the people in the region. Michener sends Chandler to a global summit to investigate this allegation, as well as rumors of a possible mutation of the original virus that has caused a fresh outbreak in Japan.

After the chilling events at the end of last season, Tom Chandler has given up his heroic titles and responsibilities and sought solace – and anonymity -- with his family in a small fishing village in Greece. Meanwhile, Captain Slattery and the crew of Nathan James have discovered that the virus has “jumped kingdoms” and now infects the world’s food crops, bringing humanity to the brink of global famine. As the ship traverses the Mediterranean in search of a solution that can save the world's food supply, Chandler encounters his own enemies in Greece. His “hero’s journey” becomes a modern day retelling of Homer’s Odyssey.

In season five, the world is finally recovering from the deadly virus that decimated the population, but global political unrest still remains. Tom Chandler has retired and his former crew has scattered. Sasha Cooper, Lieutenant Danny Green, SBS WO-N Wolf Taylor and Sergeant Azima Kandie are on a covert mission in Panama. When they are wrongly blamed for an attack on the Panamanian President, the consequences for the United States are dire. The Nathan James must fight to prevent invasion by Latin America and the next world war.