This review discusses major findings from the Women's Health Initiative Memory Study (WHIMS). WHIMS reported hormone therapy (HT) – conjugated equine estrogen (CEE) with or without medroxyprogesterone acetate (MPA) – increased the risk for dementia (HR 1.76 [95% CI, 1.19–2.60]; P =0.005) and global cognitive decline, with a mean decrement relative to placebo of 0.21 points on the Modified Mini Mental State Examination (3MS) (P =0.006) in women age 65 and older. A subset of WHIMS participants joined the ancillary WHI Study of Cognitive Aging (WHISCA) trials, in which domain-specific cognitive tests and mood were measured annually. Compared with placebo, CEE+MPA had a negative impact on verbal memory over time (P =0.01); and CEE-Alone was associated with lower spatial rotational ability (P ≤0.01) at the initial assessment, but the difference diminished over time. The ancillary WHIMS-MRI study measured subclinical cerebrovascular disease to possibly explain the negative cognitive findings reported by WHIMS and the increased clinical stroke in older women reported by the WHI. WHIMS-MRI reported that while CEE+MPA and CEE-Alone were not associated with increased ischemic brain lesion volume relative to placebo; both CEE+MPA and CEE-Alone were associated with lower mean brain volumes in the hippocampus (P =0.05); frontal lobe (P =0.004); and total brain (P =0.07). HT-associated reductions in hippocampal volumes were greatest in women with baseline 3MS scores ≤90.