Significant advances have occurred in our understanding of the biology, immunology, and immunopathology of the usually asymptomatic human infection by the intestinal parasite, Strongyloides stercoralis. Factors that increase the risk for the occurrence of symptomatic intestinal hyperinfection and/or often-fatal disseminated strongyloidiasis have been better defined. The pathophysiology underlying these risk factors, whether disease-related or iatrogenically induced, is a compromised immune system leading to dysfunction of TH-2 helper cells. These specialized lymphocytes are central to maintaining the delicate balance that exists between the infected human host and the stabilized parasite. Recognition of risk factors that impair the function of TH-2 lymphocytes is essential to heightening the index of clinical suspicion enhancing earlier, accurate diagnosis, and the introduction of appropriate therapy. This review summarizes what is understood about infection by S. stercoralis; its focus will be on the epidemiology, diagnosis, clinical presentation patterns in the immunocompetent and immunocompromised human hosts, and recommended treatment regimens.