During acute infection with the parasiteTrypanosoma cruzi,the causal agent of Chagas’ disease, tissue damage is related to intense tissue parasitism. Here we discuss histological approaches for an optimal visualization and quantification ofT. cruzinests in the heart, the main target organ of the parasite. These analyses are important to evaluate the course of the infection in different experimental models and also can be used to investigate parasite colonization and inflammatory processes in other infected tissues and biopsies.