This article introduces the tools and terminology used for the classification of specific isolates of the Mycobacterium tuberculosis complex (MTC). The utility of these tools and terminology is illustrated by discussing work from independent laboratories that have established a genome-based phylogeny for the MTC. It considers the use of these markers to distinguish atypical isolates not conforming to attributes of traditional MTC members. Finally, it discusses the current genomic evidence regarding the origin and evolution of M. tuberculosis in the context of its relevance for tuberculosis control in humans and other mammalian hosts.