One of the most relevant issues beyond the effectiveness of etiological treatment of Chagas disease is the lack of consensual/feasible tools to identify and certify the definitive parasitological cure. Several methods of distinct natures (parasitological, serological, and molecular) have been continuously proposed and novel perspectives are currently under investigation. Although the simultaneous use of distinct tests may offer better contributions and advances, it also leads to controversies of interpretation, with lack of mutual consent of cure criterion amongst researchers and physicians. In fact, when distinct host compartments (blood/tissues) are evaluated and explored, novel questions may arise due to the nature and sensitivity limit of each test. This short analytical review intends to present a chronological and critical overview and discuss the state-of-the-art distinct devices available for post therapeutic cure assessment in Chagas disease, their contributions, meanings, and interpretation, aiming to point out the major gaps and propose novel insight for future perspectives of post therapeutic management of Chagas disease patients.