Buffalo Niagara International Airport is the main airport in the region. Continental Airlines affiliates fly direct to and from New York City (Newark Liberty International Airport) and Albany, with connections from the latter to Long Island (Islip), Adirondack Regional Airport, and the Plattsburgh airport. JetBlue Airlines has service between Buffalo and New York City's JFK International Airport, Northwest Airlines flies to Newark, and American Airlines flies into LaGuardia Airport. US Airways flies into Albany and LaGuardia.
Another option, especially if you plan to tour the eastern part of the region, is to fly into the Greater Rochester International Airport, rent a car, and drive the rest of the way.