The pathology of Chagas disease presents a complicated and diverse picture in humans. The major complications and destructive evolutionary outcomes of chronic infection by Trypanosoma cruzi in humans include ventricular fibrillation, thromboembolism and congestive heart failure. Studies in animal models and human patients have revealed the pathogenic mechanisms during disease progression, pathology of disease and features of protective immunity. Accordingly, several antigens, antigen-delivery vehicles and adjuvants have been tested to elicit immune protection to T. cruzi in experimental animals. This review summarizes the research efforts in vaccine development against Chagas disease during the past decade.