As seen in:
12 Monkeys, The Stand, 28 Days Later, Omega Man, Michael Crichton's The Andromeda Strain, Outbreak.
How it goes down:
It might be a single, momentous "oops" in the sterile silence of a laboratory. Or, it might be a deliberate attack by a vicious and extremely short-sighted terrorist group. But when patient zero finally leans against you on the bus and sneezes down your neck, humanity will be six Kleenex "Ultra Aloe" boxes from extinction.
Society breaks apart as policemen get the sniffles, and the army is stretched thin. Cities burn as diseased rioters rage through the streets. Miracle cures pop up on every corner, and only stop when everyone in the neighborhood is too sick to get out of a bed filled with vomit and their own intestines. With not enough able-bodied people to manufacture goods or run the farms, the infrastructure breaks down and the survivors are left to battle it out in a post-apocalyptic battle royale.
Why it kicks ass:
Everyone assumes they'll be among the 1 percent who are immune to the plague. They'll be left in a quiet world where all the annoying people are gone, but all of their cars and stereos have been left behind. You and your friends can go play softball at a deserted Yankee Stadium, then take to the streets and fight it out with one of the roving gangs of thugs.
Chances of it happening:
Pandemics, defined by their high-contagion rate and ridiculous body count, have been rare. Famous alumni include cholera, influenza and the Bubonic plague (that last one killed 100 million fucking people, up to 20 percent of the world's population at the time). Yes, we beat those bastards, but that doesn't make us invincible.
You see, we aren't the only ones who are evolving. Some types of Tuberculosis have kicked our current batch of antibiotics in the crotch, and since many pharmaceutical companies are more interested in filling our cabinets with lifestyle-enhancing drugs than new types of antibiotics, we may not have the meds to fight off the next pandemic that comes along.
We've got more people, living closer together, and routinely traveling across oceans. One business traveler gets infected and it could spread like wildfire.
How to survive it (according to movies on the topic):
Many believe that, right before things reach the point of no return, some misfit scientists will discover the cure and will have to race to get the vial to the lab and maybe wind up hanging off a helicopter in the process.
However, most sources found at our local video store simply depict the pandemic as already having happened, leaving only a select few survivors behind. So, either there is no hope of stopping one once it starts, or else we won't try very hard in hopes a peopleless world will finally give us the chance to ride a motorcycle through the Louvre.