The complexity of Chagas disease is still a challenge in endemic regions and an emergent public health problem
in non-endemic countries. The causative agent of this neglected tropical disease, Trypanosoma cruzi, is mainly transmitted
by triatomine vectors and possesses multiple epidemiologically important strains. Current chemotherapeutics are outdated
and their limited efficacy is one of the major reasons for treatment discontinuation. In this context, it is urgent the
development of novel, safe and economically accessible antichagasic drugs. Various classes of heterocycles and natural
compounds have been described as potential antichagasic scaffolds, and coumarins are no exception. These versatile
compounds have a wide spectrum of biological activities, and numerous natural and synthetic coumarins have been reported
with antichagasic potential. The aim of this review is to discuss the available literature between 2001 and 2020 regarding
natural and synthetic coumarins with anti-Trypanosoma cruzi activity. Moreover, some of the studies herein comprised are
dedicated to the potential of coumarins to inhibit promising targets in Trypanosoma cruzi.