Tuberculosis (TB) cases worldwide have declined over the last 10 years, but strong barriers to detection and treatment of TB still exist, especially among 2 special subgroups of low-income populations, immigrants and the homeless, where the incidence of TB can be up to 20 times higher than the general population even in affluent countries. A systematic review of literature was performed, aimed at identifying the main (1) barriers to and (2) effective interventions for the improved detection and treatment of TB in homeless and immigrant populations. Data were collected from 22 studies out of 80 potentially relevant citations worldwide published between 1998 and 2012. Key findings show that hard-to-reach groups like immigrants and the homeless seem willing to obtain care if they believe it is important, but any new detection/treatment efforts must go beyond current bio-medical models to bio-psychosocial models of the target populations' cultural values. Preliminary results also suggest that the best interventions for the homeless and immigrant populations will be a combination of, at least, monetary incentive and improved accessibility of care.