Nonalcoholic fatty liver disease (NAFLD) prevalence in women is increasing worldwide. Women of reproductive age have lower rates of NAFLD compared with men; however, this protection is lost following the menopausal transition when NAFLD prevalence in postmenopausal women becomes similar to or surpasses that in age-matched male counterparts. Ongoing epidemiological, clinical, and experimental studies indicate greater NAFLD risk and higher rates of severe hepatic fibrosis in postmenopausal women relative to premenopausal women, and that older women with NAFLD experience greater mortality than men. Investigations involving ovariectomized animal models demonstrate a causal relationship between estrogen deficiency and heightened susceptibility to the development of fatty liver and steatohepatitis, although dietary factors may exacerbate this complex relationship. The accumulated findings suggest that a better understanding of the interplay among menopausal status, metabolic comorbidities, and sex steroids in NAFLD pathogenesis is needed. Further, the mechanisms underlying the difference in NAFLD risk between postmenopausal and premenopausal women remain incompletely understood. The goals of this review are to summarize studies of NAFLD risk in postmenopausal women, discuss results from animal models of estrogen deficiency, and explore the development of NAFD within the context of altered sex hormone profiles resulting from the menopausal transition. Potential implications for the prevention, diagnosis, and treatment of NAFLD in this relatively understudied cohort are also addressed.