Despite the smaller genome sizes present in the pathogenic Mycobacteria, and the resulting background of orthogroup loss in the evolution towards pathogens, we observe significant expansions in certain gene families in the pathogenic Mycobacteria and the Mtb complex relative to non-pathogenic relatives. We also observe evidence for selection in certain families on branches leading to the pathogenic Mycobacteria, the Mtb complex, and the soildwelling Mycobacteria.