Host-directed therapies (HDTs) to increase host control of Mycobacterium tuberculosis and limit the pathology caused by tuberculosis (TB) have advanced from the laboratory to the clinic. Several of these HDTs are repurposed drugs, which provide significant advantages over lengthy and costly traditional drug discovery approaches. This review covers the preclinical, retrospective clinical, and randomized controlled trial (RCT) evidence supporting the rapid repurposing of drugs for use as TB HDTs. We explore classes of potential HDTs by preclinical mechanism of action to identify cases where the concept of the therapy is sound, but the current availability of therapeutic agent is lacking. Apart from the drugs that have progressed through to RCTs, we highlight drugs with strong preclinical and retrospective portfolios that may form the next wave of trial candidates. Overall, HDTs are poised to contribute to a reduction in the global burden of TB and posttreatment lung disease.