Ovarian hyperstimulation syndrome (OHSS) is a significant adverse consequence of ovarian stimulation in assisted reproduction technology (ART) treatment, which may threaten the life of patients in its severe form. OHSS is believed to be mainly due to an excessive response to ovarian stimulation. The molecular pathophysiological reactions of OHSS remain mostly unresolved, but several potential signaling pathways have been identified, with OHSS signaling pathways activated by either exogenous or endogenous human chorionic gonadotropin (hCG). Several counteractive strategies have been implemented in clinical practice to prevent this potentially life-threatening condition, with at least 40 published studies proposing different interventions. Freeze-all IVF and starting gonadotropin dose individualization, depending on patient-specific variables, are cornerstone interventions suggested for the prevention of OHSS, with their implementation making OHSS-free clinics a real possibility in the future.