In this chapter, we review and update current knowledge about the evolution, systematics, and biogeography of the Triatominae (Hemiptera: Reduviidae)-true bugs that feed primarily on vertebrate blood. In the Americas, triatomines are the vectors of Trypanosoma cruzi, the etiological agent of Chagas disease. Despite declining incidence and prevalence, Chagas disease is still a major public health concern in Latin America. Triatomines occur also in the Old World, where vector-borne T. cruzi transmission has not been recorded. Triatomines evolved from predatory reduviid bugs, most likely in the New World, and diversified extensively across the Americas (including the Caribbean) and in parts of Asia and Oceania. Here, we first discuss our current understanding of how, how many times, and when the blood-feeding habit might have evolved among the Reduviidae. Then we present a summary of recent advances in the systematics of this diverse group of insects, with an emphasis on the contribution of molecular tools to the clarification of taxonomic controversies. Finally, and in the light of both up-to-date phylogenetic hypotheses and a thorough review of distribution records, we propose a global synthesis of the biogeography of the Triatominae. Over 130 triatomine species contribute to maintaining T. cruzi transmission among mammals (sometimes including humans) in almost every terrestrial ecoregion of the Americas. This means that Chagas disease will never be eradicated and underscores the fact that effective disease prevention will perforce require stronger, long-term vector control-surveillance systems.