Abstract Objective: To present an overview of potential etiologies, clinical manifestations, and treatment modalities of premature ovarian failure (POF). Design: A search of past and current articles on basic ovarian physiology and POF with use of MEDLINE. Additional information was obtained from an active study section on POF at the National Institutes of Health. Specific sections of this manuscript summarize the strengths and weaknesses of the possible pathophysiologic processes and management options of POF as they appear in the literature. Result(s): POF is not an uncommon disorder. Although the etiology remains elusive in most cases, several rare specific causes have been discovered. Although POF was once thought to be permanent, a substantial number of patients experience spontaneous remissions. Because of the association with other autoimmune diseases, close follow-up is recommended in patients with POF. Hormone replacement therapy remains the cornerstone of treatment, and the best chance of achieving a pregnancy is through oocyte donation. Conclusion(s): An understanding of basic ovarian embryology and physiology will allow clinicians to apply current treatments and develop new innovative therapies for their patients with POF.