Will Smith in I Am Legend Courtesy of Warner Bros.

Another departure from the 1954 book is its location. The book is set in Los Angeles, but Goldsman decided to transfer the action to New York City to exploit the visual benefits that a deserted Gotham would offer.

"L.A. looks empty at three o'clock in the morning or even three o'clock in the afternoon if you get the right streets," the writer says. "New York is never empty. To me, it was just a much more interesting way of showing the windswept emptiness of a world."

But shooting a movie of this magnitude in New York City brings with it a set of logistical headaches. In late January 2007, not far from the World Trade Center's Ground Zero, the southern tip of Manhattan is made to resemble a war zone. The skies above South Street Seaport are filled with Army and Coast Guard helicopters. Military and police vehicles roll up the historic cobblestone roads. An evacuation area exists beneath the Brooklyn Bridge. In the immediate aftermath of the Sept. 11 attacks, Hollywood producers, wary that film audiences were still recovering from the shock of the events, shied away from depicting the destruction of New York City. I Am Legend changes that, showing it desolate and broken.

In order to isolate the infected and prevent the virus from spreading beyond the island of Manhattan, military jets destroy the Brooklyn Bridge. (The bridge was last wiped out on screen in 1998's Godzilla — a movie that reportedly captured the imagination of Al Qaeda leader Abu Zubaydah and inspired the terrorist leader to consider the bridge as a potential future target.)

The film's plot also resonates with fears that New York City may not be fully prepared to respond adequately to a bioterrorist attack.

Will Smith in I Am Legend Courtesy of Warner Bros.

"We know more about viruses now," Goldsman says. "We know more about what quarantine procedures might look like in a major city. We have a better understanding of medical treatments, emergency interventions. We speculated with virologists and the Centers for Disease Control (CDC), to an extent, what would happen if an outbreak happened in New York. But then we went further. We pushed so far as to quarantine the city in a kind of dramatic way where it isn't actually scientifically correct. But that was a little bit of creative license so we could do some cool stuff."

Smith claims that he wasn't worried about bioterrorism or the threat of bird flu until he visited the CDC as part of his research for the part: "It's military. We were greeted by a general. And I was joking and saying: 'What's all the seriousness around here?' And he said: 'Because we know what people don't want to admit, and it's that human beings are not the top of the food chain. Viruses are the top of the food chain.'"