Ovarian hyperstimulation syndrome (OHSS) is a potentially serious complication, predominantly iatrogenic in nature, arising from ovarian stimulation in women undergoing assisted reproductive technologies (ART). Advances in reproductive medicine have made it possible to identify individuals at heightened risk, tailor stimulation protocols accordingly, and implement interventions that target the underlying pathophysiology to minimize disease severity. Contemporary standards of care should incorporate proactive strategies to prevent and mitigate OHSS risk—before, during, and after treatment. Although most cases are iatrogenic, spontaneous occurrences of OHSS have also been documented. This chapter will examine the pathophysiological mechanisms of OHSS and highlight reported instances of non-iatrogenic presentations.