We performed a descriptive analysis of acute and potentially life-threatening tropical diseases among 82,825 ill western travelers reported to GeoSentinel from June of 1996 to August of 2011. We identified 3,655 patients (4.4%) with a total of 3,666 diagnoses representing 13 diseases, including falciparum malaria (76.9%), enteric fever (18.1%), and leptospirosis (2.4%). Ninety-one percent of the patients had fever; the median time from travel to presentation was 16 days. Thirteen (0.4%) patients died. Ten patients had falciparum malaria, 2 patients had melioidosis, and 1 patient had severe dengue. Falciparum malaria was mainly acquired in West Africa, and enteric fever was largely contracted on the Indian subcontinent; leptospirosis, scrub typhus, and murine typhus were principally acquired in Southeat Asia. Western physicians seeing febrile and recently returned travelers from the tropics need to consider a wide profile of potentially life-threatening tropical illnesses, with a specific focus on the most likely diseases described in our large case series.