Hormonal contraceptives (HCs) are one of the most widely used classes of drug worldwide and are a critical part of women's health. Beyond their primary use for birth control, HCs exert many health benefits, including treatment of menstrual-related symptoms and reduced risk of certain types of cancers. Here, we focus on the role of HCs in promoting resilience to depression and Alzheimer's disease. Although risks for depression with HC use have been widely stated, HCs only increase risk for up to 10 % of users, and conversely improve mood and protect against depression for many others. Emerging evidence also suggests that HC use protects against age-related cognitive decline and Alzheimer's disease, even decades after HC use. We propose that these effects are due to modulatory effects of HCs on stress-related signaling and neuroimmune function. In this paper, we discuss how HCs interact with stress responsivity, neuroimmune signaling, and other individual differences to promote resilience or susceptibility to psychiatric and neurological disorders.