Host-directed therapies are a relatively new and promising approach to treatment of tuberculosis. Modulation of specific host immune pathways, including those that impact inflammation and immunopathology, can limit mycobacterial infection and pathology, both in cell culture and in animal models. This review explores a range of host pathways and drugs, some already approved for clinical use that have the potential to provide new adjunctive therapies for tuberculosis. Drugs targeting host processes may largely avoid the development of bacterial antibiotic resistance, a major public health concern for tuberculosis. However, these drugs may also have generally increased risk for side effects on the host. Understanding the specific mechanisms by which these drugs act and the relationship of these mechanisms to Mycobacterium tuberculosis pathogenesis will be critical in selecting appropriate host-directed therapy. Overall, these host-directed compounds provide a novel strategy for antituberculosis therapy.