We present an overview of the two main strategies for the primary (vector control) and secondary (patient care) prevention of Chagas disease (CD). We identify major advances, knowledge gaps, and key research needs in both areas. Improved specific chemotherapy, including more practical formulations (e.g., paediatric) or combinations of existing drugs, and a better understanding of pathogenesis, including the relative weights of parasite and host genetic makeup, are clearly needed. Regarding CD vectors, we find that only about 10–20% of published papers on triatomines deal directly with disease control. We pinpoint the pitfalls of the current consensus on triatomine systematics, particularly within the Triatomini, and suggest how some straightforward sampling and analytical strategies would improve research on vector ecology, naturally leading to sounder control-surveillance schemes. We conclude that sustained research on CD prevention is still crucial. In the past, it provided not only the know-how, but also the critical mass of scientists needed to foster and consolidate CD prevention programmes; in the future, both patient care and long-term vector control would nonetheless benefit from more sharply focused, problem-oriented research.