Elispot has been used as an important tool for detecting immune cells' products and functions and has facilitated the understanding of host-pathogen interaction. Despite the incredible diversity of possibilities, two main approaches have been developed: the immunopathogenesis and diagnosis/prognosis of infectious diseases as well as cancer research. Much has been described on the topics of allergy, autoimmune diseases, and HIV-Aids, however, Elispot can also be applied to other infectious diseases, mainly leishmaniasis, malaria, some viruses, helminths and mycosis usually classified as tropical diseases. The comprehension of the function, concentration and diversity of the immune response in the infectious disease is pointed out as crucial to the development of infection or disease in humans and animals. In this review we will describe the knowledge already obtained using Elispot as a method for accessing the profile of immune response as well as the recent advances in information about host-pathogen interaction in order to better understand the clinical outcome of a group of tropical and neglected diseases.