Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in developed countries and is increasing in prevalence with the rise of diabetes and obesity. In addition to obesity and age, gender may also influence the prevalence and severity of NAFLD. However, mechanisms underlying gender-based differences in NAFLD have not been clearly defined. Furthermore, alterations in body composition, fat distribution and/or hormonal or metabolic changes that occur following menopause and in the setting of polycystic ovary syndrome may influence the development and progression of NAFLD. In this article, we will summarize known gender differences as well as the proposed mechanisms for gender differences in NAFLD, review two women-specific issues that may influence the prevalence and severity of NAFLD, menopause and polycystic ovary syndrome, and discuss potential therapeutic options for women with NAFLD who are postmenopausal or have polycystic ovary syndrome.