Trypanosomatidae family, an exclusively parasitic taxon that infects a broad spectrum of animals and plants, and the Bodonidae family, exclusively free-living organisms. Several biological characteristics are important for understanding T. cruzi, a parasite with broad heterogeneity and biological plasticity. The pioneering studies by Carlos Chagas and Brumpt already called attention to these characteristics, which represent an epidemiological maze even to this day. The heterogeneity of T. cruzi, expressed by various biological, biochemical (differences in the infection pattern in mice and growth in axenic culture, differences in the capacity to colonize culture cells, and drug resistance, among others), and molecular markers results in the parasite's wide distribution in nature in distinct epidemiological scenarios. In fact, T. cruzi is capable of infecting more than a hundred species of mammals and nearly all their tissues. Another important aspect of T. cruzi biology involves the parasite's multiple transmission mechanisms, e.g., transfusional, congenital, and oral, and by contamination of the skin and mucosa by feces of triatomines carrying the infective forms, called metacycical trypomastigotes. T. cruzi is also a generalist parasite in relation to the vector, since it infects dozens of triatomine species from the Reduviidae family. The biological plasticity of T. cruzi results in transmission cycles in nature that are characterized as multivariate, complex, and peculiar on a spatial and temporal scale. This complexity means that the human host probably entered into contact with the parasite on different occasions over time and by different routes, depending mainly on interaction with the environment, that is, the ways by which the host was exposed to infection. Since the pioneering work of Carlos Chagas, researchers have attempted to establish a correlation between some genotypic or phenotypic characteristic of the parasite and the disease profile, local epidemiological characteristic, or association with the vector or animal reservoir. Although many aspects of T. cruzi biology and ecology are known, there are still numerous unanswered questions. Scientists have never succeeded in robustly correlating a given type of isolate with the disease or its epidemiology.