The Ovarian Hyperstimulation Syndrome (OHSS) represents one of the biggest nightmares of all physicians involved in Assisted Reproductive Technologies (ART). Every year, several hundreds of women are hospitalized and to date several deaths have been reported. The pivotal event in the development of OHSS is the disruption of capillary integrity that results in leakage of intravascular fluid and proteins into third space. On the molecular level, human chorionic godadotropin (HCG) either exogenous or endogenous, functions as the triggering point for the production of vascular endothelial growth factor (VEGF) that is the main mediator to increase permeability on the vascular bed. Spontaneous OHSS has also been reported, either due to inappropriate activation of a mutant FSH receptor or due to very high levels of HCG during pregnancy. The available evidence on the several preventive and therapeutic approaches with special attention to level 1 evidence when available is also presented. OHSS is a self-resolving condition and the main role of the physician is to correct and maintain the intravascular volume, to support renal function and respiration and prevent thrombotic events. An algorithm on the management of OHSS on an outpatient basis and in the hospital is based on the previous mentioned principles.