Chagas' disease (CD) is one of the most important neglected tropical disorders, being a major health concern in Latin America. CD is caused by the protozoan parasite Trypanosoma cruzi, which is typically spread by triatomine bugs. Despite the progress achieved in the study of this protozoon, there is no effective treatment available for CD. The current chemotherapy is based on old and quite unspecific drugs that provide unsatisfactory results, suffer from considerable side effects and present a lack of efficacy and specificity against all stages of the disease. In the search for pharmacological control of CD, bioactive organometallic compounds appear as attractive alternatives for the production of new anti-chagasic agents. Although the rational design of organometallic compounds with good therapeutic index is still under development, a number of potential metal-based antiparasitic drugs have been reported. This paper reviews the latest advances in the design of organometallic compounds that proved to be active against CD.