An estimated 100 million people in the Latin American and Caribbean (LAC) region live on less than US$2 per day, while another 46 million people in the US live below that nation's poverty line. Almost all of the 'bottom 100 million' people suffer from at least one neglected tropical disease (NTD), including one-half of the poorest people in the region infected with hookworms, 10% with Chagas disease, and up to 1-2% with dengue, schistosomiasis, and/or leishmaniasis. In the US, NTDs such as Chagas disease, cysticercosis, toxocariasis, and trichomoniasis are also common among poor populations. These NTDs trap the poorest people in the region in poverty, because of their impact on maternal and child health, and occupational productivity. Through mass drug administration (MDA), several NTDs are on the verge of elimination in the Americas, including lymphatic filariasis, onchocerciasis, trachoma, and possibly leprosy. In addition, schistosomiasis may soon be eliminated in the Caribbean. However, for other NTDs including hookworm infection, Chagas disease, dengue, schistosomiasis, and leishmaniasis, a new generation of 'anti-poverty vaccines' will be required. Several vaccines for dengue are under development by multinational pharmaceutical companies, whereas others are being pursued through non-profit product development partnerships (PDPs), in collaboration with developing country manufacturers in Brazil and Mexico. The Sabin Vaccine Institute PDP is developing a primarily preventive bivalent recombinant human hookworm vaccine, which is about to enter phase 1 clinical testing in Brazil, as well as a new therapeutic Chagas disease vaccine in collaboration with several Mexican institutions. The Chagas disease vaccine would be administered to seropositive patients to delay or prevent the onset of Chagasic cardiomyopathy (secondary prevention). Together, MDA and the development of new anti-poverty vaccines afford an opportunity to implement effective control and elimination strategies for the major NTDs in the Americas.