Premature ovarian failure (POF) generally describes a syndrome consisting of amenorrhea, sex steroid deficiency, and elevated/menopausal levels of ganadotropins in a woman aged more than two standard deviations below the mean age at menopause estimated for the reference population. Numerous questions relating to this condition remain unanswered, and several important management issues are yet to be addressed. The challenges posed by this important condition range from difficulties with nomenclature to the absence of standardized diagnostic criteria and management guidelines. In the present paper we discuss the management of spontaneous premature ovarian failure, highlight the challenging issues, review the current literature and propose a practical management outline based on our local practice. Women with POF have unique needs that require special attention. There is an urgent need for a more suitable terminology and evidence-based guidelines on which to establish the diagnosis and manage this difficult condition.