Decision-making plays a pivotal role in daily life as impairments in processes underlying decision-making often result in an inability to make profitable long-term decisions that incorporate expectations of future outcomes. In case of pathological gambling such impairments appear to be present as subjects continue to gamble despite the fact that this activity disrupts their personal, professional or financial life. Both from a research and treatment point of view, an important issue is whether differences between men and women exist in the tendency to engage in gambling as a leisure activity and to develop pathological gambling. I will discuss that differences between male and female subjects may exist regarding the trajectory towards pathological gambling: when considered in aggregate, there appears to be a (slightly) elevated risk for gambling problems or severity of gambling in men compared to women. These differences seem to be due to a complex interaction of genetic make-up, effects of the (social) environment on risk-taking behaviour, stress-related changes in risk-taking, and personality/information-processing characteristics related to decision-making. These different factors will be discussed. Future studies should address the interaction between these factors using among others ecologically valid research methods.