Unsustainable levels of road avoidance or mortality result in the barrier effect, and therefore habitat fragmentation, disrupting metapopulation dynamics and potentially leading to genetic isolation. As ecological behaviors of snakes vary interspecifically, responses of snakes when encountering roads would also be expected to vary interspecifically. The probability of crossing the road significantly varied across species of southeastern U.S. snakes, with smaller species of snakes avoiding the road almost completely. In addition to crossing rates, species were significantly different in crossing speed and responses to a passing vehicle. Venomous snakes crossed the road more slowly than nonvenomous species or species that rely on flight for defense. However, all species crossed the road at a perpendicular angle, minimizing the time spent crossing. Scientific identification of particular vulnerabilities of snake species to roads is essential to mitigate wildlife impacts of existing roads and to design transportation systems effectively in the future.