New tools for controlling tuberculosis are urgently needed. Despite our emerging understanding of the biogeography of Mycobacterium tuberculosis, the implications for development of new diagnostics, drugs, and vaccines is unknown. M tuberculosis has a clonal genetic population structure that is geographically constrained. Evidence suggests strain-specific differences in virulence and immunogenicity in light of this global phylogeography. We propose a strain selection framework, based on robust phylogenetic markers, which will allow for systematic and comprehensive evaluation of new tools for tuberculosis control.