Use of postmenopausal estrogen has changed since the release of the first results from the Women's Health Initiative in 2002. Professional organizations, the US Food and Drug Administration, and the US Preventive Services Task Force have issued new recommendations against use of estrogen and progestin or progesterone for prevention of chronic conditions. This article applies the current state of evidence for postmenopausal estrogen use to management decisions in 2 clinical scenarios initiating therapy in a perimenopausal woman with hot flashes and discontinuing estrogen use in a long-term user.