This novel centers on a world-changing virus that reanimates dead tissue to allow the dead to walk. Central to the story is the life of Hannah Winter, head of information technology at Biogenetics & Disease Control, a medical research company located underground in the city of Dulce, New Mexico. Nearing December 21, 2012, the end of the Mayas Long Count calendar, the story begins in Chiapas, Mexico, where a raccoon with a fast-evolving strain of rabies has attacked a couple of campers. The woman dies from a deep neck wound. The raccoon bites the man, who then kills the raccoon with a tire iron. The man, now infected, transforms into a zombie. He spreads the virus by biting a truck driver and a woman who is selling fruit.

Not knowing zombies are in the area, nineteen-year-old Jenna Winter, Hannah's sister, enters a Starbucks restaurant in San Antonio, Texas, to buy a double-shot vanilla latte with soy milk. An out-of-control bus totals her car, and customers fleeing the store trample on her cell phone until it's broken. Jenna flees the vicinity, where police officers are shooting at zombies, eventually finding shelter in a hotel for the night. Jenna telephones Hannah, who persuades her to find a way to be with her in New Mexico, the safest place under the circumstances. Julie Mehta, a Biogenetics & Disease Control virologist, works to find an antidote for the plague of the century. She performs laboratory tests on whole brain specimens of the infected, which are acquired by company security guards.