Trypanosoma cruzi has a complex life cycle that involves a vertebrate as well as an invertebrate host. In this, last two stages are present: trypomastigotes, the flagellated and infective stage and the amastigote, which is the replicative stage. T. cruzi is considered one of the most successful intracellular parasites, because it cannot be eliminated by the immune system and has the capacity of invading, surviving, and replicating inside the host cells. The effects that the infection has over the immune system have been widely studied at the molecular and cellular level. However, understanding the mechanisms that the parasite uses to evade the immune system to persist in the infected individual is necessary for the effective development of drugs and/or vaccines. In this chapter, a compilation of the already described mechanisms will be carried out.