Quinine is still frequently used by practitioners for the treatment of nocturnal leg cramps, despite the lack of Food and Drug Administration (FDA) approval. We report the 15th case of quinine-induced hemolytic-uremic syndrome (HUS) in the medical literature. The likely mechanism by which quinine induces HUS is via quinine-dependent antibodies to blood cellular constituents. These antibodies likely cause endothelial damage and the resultant nephropathy, microangiopathic hemolytic anemia, and thrombocytopenia that define HUS. Although there is no set guideline for the treatment of quinine-induced HUS, most authorities consider plasmapheresis as the standard of care, especially in severe cases. Our patient required the longest known treatment duration (16 plasmapheresis treatments over a 37-day period) for disease resolution. The prognosis of quinine-induced HUS is excellent, with no deaths reported in the literature.