The Keys are regularly threatened by tropical storms and hurricanes, leading to evacuations to the mainland. Untouched for many years, a carefree attitude led many residents to view "mandatory" evacuations as "voluntary" and "voluntary" evacuation orders as nothing at all. The attitude proved dangerous when Hurricane Georges (pronounced zhorzh in French), after tearing up much of the Caribbean, caused damage and extensive flooding in the Lower Keys in 1998, before making landfall in Mississippi.

Tropical cyclones present special dangers and challenges to the entire Keys. Because no area of the islands is more than 20 feet above sea level (and many are only a few feet elevation), and water surrounds the islands, nearly every neighborhood is subject to devastating flooding as well as hurricane winds.

Because of the threat from storm surge, evacuations are routinely ordered when the National Weather Service issues a hurricane watch or warning, and are sometimes ordered for a tropical storm warning. Evacuation of the Keys depends on causeways and the two-lane highway to the mainland. Time estimates for evacuating the entire Keys range from 12 to 24 hours. Evacuation estimates are significant in emergency planning, of course, but also because they are a factor in local and state regulations for controlling development. The building permit allocation was increased in 2005 when local governments reduced estimates for evacuation.

In the active hurricane seasons of 2004 and 2005, the Keys were under mandatory evacuation orders several times. In August, 2004, Hurricane Charley passed about 70 miles west of Key West, bringing tropical storm winds to the lower keys. The lower keys were evacuated in preperation for Hurricane Ivan in September, 2004 and Hurricane Dennis in July, 2005, but neither hurricane came close enough to the Keys to do much damage. Hurricane Katrina, which went on to devastate parts of Louisiana and Mississippi, moved through south Florida in August, 2005 and tracked southwest past Key West, causing minor damage and flooding. Hurricane Rita, which went on to destroy parts of Louisiana and Texas, grew from a tropical storm to a Category 2 hurricane as it moved westward from the Bahamas, passing south of Key West and causing damage and surge flooding as far north as Key Largo. In October, 2005, Hurricane Wilma became the most devestating hurricane to hit the Keys in decades when it passed just northwest of Key West. The city was left under 3 to 6 feet (1 to 2 metres) of water from the storm surge, and major flooding was reported throughout the Keys up to Key Largo.

The waters surrounding the Keys are part of a protected area known as the Florida Keys National Marine Sanctuary.