Current evidence suggests that post-adolescent acne in women is on the rise. Acne in this subgroup of patients commonly follows a specific pattern that can often be treatment resistant and/or prone to relapse, including after oral isotretinoin therapy. With a plethora of medications to choose from for acne treatment, many of which have been used in the past by patients without success, dermatology practitioners often find oral contraceptives and spironolactone to be of benefit in otherwise healthy adult females. Also, some of these patients may have concurrent hormonal anomalies such as polycystic ovarian syndrome or other underlying endocrine disorders, which should also be appropriately worked up by the clinician and managed accordingly. This article reviews some of the underlying pathophysiological factors, available treatment options, and screening guidelines to assist clinicians in the management of acne in adult females.