The major neglected parasitic infections in the US include Chagas disease, cysticercosis, toxocariasis, toxoplasmosis, and trichomoniasis. These five parasitic infections are considered “neglected” based on their high prevalence, chronic and disabling features, and their strong links with poverty. In contrast, the major intestinal parasitic infections found in the US—cryptosporidiosis, cyclosporiasis, and giardiasis—are mostly acute diarrheal illnesses without significant links to poverty or neglected populations. This review highlights new information (mostly from the last five years) on the major neglected parasitic infections affecting impoverished Americans, with respect to their distribution and unique clinical presentations as well as their surprising links to cardiovascular, respiratory, and neuropsychiatric conditions ordinarily thought of as noncommunicable diseases. Key diagnostic and therapeutic challenges and urgent needs for active surveillance and prevention are also presented.