The survival of Mycobacterium tuberculosis (M. tuberculosis) in the host is largely attributed to its ability to resist acidic environment within macrophages. M. tuberculosis inhibits the fusion of phagosomes with lysosomes, thus arresting the maturation and acidification process of phagosomes. Also, the bacterium resists the killing within the acidic phagosome-lysosome compartment. Here, the current understanding of the acidification of phagosomes and M. tuberculosis acid resistance mechanisms is reviewed.