Neglected tropical diseases (NTDs) share certain traits: they are parasitic infections, prevailing in tropical environments and affecting marginalized sectors of the population. Six NTDs – ascariasis, cysticercosis, echinococcosis, hookworm infection, onchocerciasis and trichuriasis – all of them endemic in Latin America and the Caribbean (LAC), are analysed in this work. This review aims to discuss key information on the function of excretory/secretory (E/S) proteins from these parasites in their infectivity, pathogeny and diagnosis. The modulation of the host immune system to favour the permanence and survival of the parasite is also discussed. An updated knowledge on the function of E/S molecules in endemic parasitoses in LAC may lead to new approaches for the clinical management and diagnosis of these diseases. In turn, this could allow us to optimize their treatment and make it more affordable – a relevant goal given the economic constraints that the region is facing.