For humans and many other animals, gender is a fact of life. Most individuals are born either male or female and their sex will have an enormous influence on their behaviour, physiology and life history. In this review, I consider the effect gender has on lifespan. In particular, I discuss the role played by behaviour, immunity and oxidative damage in determining sex-dependent differences in longevity. I consider existing explanations for the effect of gender on lifespan and how these explanations fit together. Finally, I expand on the recent suggestion of a key role for the insulin/IGF-1 signalling pathway in regulating sex-dependent differences in lifespan(1) and I highlight a number of areas for future investigation. BioEssays 29:795–802, 2007. © 2007 Wiley Periodicals, Inc.