Pelvic organ prolapse, including anterior and posterior vaginal prolapse, uterine prolapse, and enterocele, is a common group of clinical conditions affecting millions of American women. This article, designed for the practicing clinician, highlights the clinical importance of prolapse, its pathophysiology, and approaches to diagnosis and therapy. Prolapse encompasses a range of disorders, from asymptomatic altered vaginal anatomy to complete vaginal eversion associated with severe urinary, defecatory, and sexual dysfunction. The pathophysiology of prolapse is multifactorial and may operate under a “multiple-hit” process in which genetically susceptible women are exposed to life events that ultimately result in the development of clinically important prolapse. The evaluation of women with prolapse requires a comprehensive approach, with attention to function in all pelvic compartments based on a detailed patient history, physical examination, and limited testing. Although prolapse is associated with many symptoms, few are specific for prolapse; it is often challenging for the clinician to determine which symptoms are attributable to the prolapse itself and will therefore improve or resolve once the prolapse is treated. When treatment is warranted based on specific symptoms, prolapse management choices fall into 2 broad categories: nonsurgical, which includes pelvic floor muscle training and pessary use; and surgical, which can be reconstructive (eg, sacral colpopexy) or obliterative (eg, colpocleisis). Concomitant symptoms require additional management. Virtually all women with prolapse can be treated and their symptoms improved, even if not completely resolved.