Within our set of organisms, we examine the evolution of pathogenicity, moving from the soil-dwelling Mycobacteria up to the intracellular parasites of the Mtb complex. We see expansions of many known gene families related to pathogenicity (PE/PPE genes, antibiotic resistance genes, genes involved in the synthesis of the mycolic acid coat, MCE genes, and Esx genes). By similarity of phylogenetic profiles, we can predict likely candidates for novel gene families related to pathogenicity. For example, we see similar expansions in gene families related to biosynthesis of molybdopterin. We further observe evidence of positive selection on molybdenum-related genes, providing further support for the importance of molybdenum in these pathogens. On the branch leading to the pathogenic Mycobacteria, we also observe evidence for positive selection in genes related to replication, recombination, and repair. It is possible that these DNA repair-related processes give the pathogenic Mycobacteria an advantage when dealing with the assault on its DNA by macrophage-generated reactive oxygen and nitrogen intermediates.