Aging and alcohol exert marked effects on the endocrine system - in particular the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) axes. The aging female brain represents a unique substrate for alcohol effects, given that both the HPG and HPA undergo significant changes with aging in women, making this demographic notably different from both males and younger females. Little attention has been directed at alcohol effects in this group but changing trends in women's drinking have brought these issues to the forefront. Major gaps in our understanding of aging females include how stressors common to middle and older aged women impact alcohol consumption, and how alcohol consumption in older women impacts brain health and aging. Thus, here we review the current state of knowledge concerning the unique neuroendocrinology of aging females, their stressors and pharmacokinetic reactions to alcohol, and their interactions as causes and neurotoxic consequences of excessive alcohol drinking. We highlight the role of the neuroimmune system at the intersection of aging, alcohol and stress effects, and brain endocrine systems. We conclude that therapeutic interventions should be aimed at managing alcohol-induced neuroimmune responses and their downstream effects on vulnerable white matter. In addition, mid-life represents a window of opportunity in which to introduce strategies to limit alcohol consumption and its consequences for the aging female brain. As so little is known about how alcohol intake impacts brain health in females, let alone in aging females, we assert the need for further investigation of middle-aged and aged females in human and preclinical studies.