Inhibition of phagolysosome biogenesis in infected macrophages is a classical pathogenesis determinant of Mycobacterium tuberculosis. In this review we primarily cover the cellular mechanisms of M. tuberculosis phagosome maturation arrest. A detailed picture is beginning to emerge, involving regulators of membrane trafficking in mammalian cells and phagosomal interactions with endosomal organelles and the trans-Golgi network. We also present a hypothesis that overlaps may exist between the mycobacterial interference with the host cell membrane trafficking processes and the targeting of the late endosomal sorting machinery by HIV during viral budding in macrophages. We propose that interference with the endosomal sorting machinery contributes to the synergism between the two significant human diseases--AIDS and tuberculosis.