Mycobacterium tuberculosis (M. tb) is one of the world's most successful human pathogens, infecting ~2 billion people worldwide. Although there are effective drugs against M. tb., the disease remains out of control owing to prolonged and toxic treatment. Shorter regimens are urgently required to control TB. Drug-resistant TB (DR-TB) also threatens to derail TB control. These unfulfilled needs could be addressed by the identification and development of host-directed therapeutic agents for TB. Manipulation of the innate immune response, including autophagy, may lead to the identification of cellular pathways that could be exploited to develop host-directed therapeutic interventions. Host-directed therapies (HDTs) aim to augment immune mechanisms against M. tb infection and/or reduce excess inflammation, thus preventing end-organ tissue damage, preserving lung function and/or enhancing the effectiveness of TB drug therapy in eliminating infection. HDTs may also have additional advantages for patients with TB/HIV co-infection, as HDTs may reduce the risk of interaction with antiretroviral drugs and the risk of developing immune reconstitution inflammatory syndrome (IRIS) and death. In this review, we discuss the role of autophagy as a potential pathway that could be exploited as a host-directed TB therapeutic agent.