In contrast to other helminthic parasites, Strongyloides stercoralis can replicate within humans, causing a chronic persistent infection that can be severe and fatal in compromised hosts. This article reviews new developments to help meet the clinical challenges of this infection, including clinical clues to the diagnosis, new diagnostic methods, including stool culture and serological assays, new drugs such as albendazole and ivermectin, and difficult treatment issues. The other major intestinal nematode parasites, including Ascaris, hookworm, and Trichuris, are extremely common worldwide, but in North America their clinical presentation is often more subtly related to low-grade worm burdens or allergic manifestations. Special consideration is given to difficult management issues, including the patient with unexplained eosinophilia, the pregnant patient, and the patient who passes a worm.