Background Current anti-tuberculosis therapeutics are not sufficiently effective against drug-resistant tuberculosis (DR-TB), and there is a need for new drugs and therapeutic approaches. It has been proposed that repurposing clofazimine for DR-TB treatment might be one way to increase therapeutic options. Methods We conducted a systematic review of studies reporting on the efficacy and safety of clofazimine as part of combination therapy for DR-TB. Six databases and six conference abstract sites were searched from inception until April 2012. All studies involving the use of clofazimine in the treatment of DR-TB were included. Results Twelve studies, comprising 3489 patients across 10 countries, were included in this review. Treatment success ranged from 16.5% (95% CI 2.7%-38.7%) to 87.8% (95% CI 76.8%-95.6%), with an overall pooled proportion of 61.96% achieving treatment success (95% CI 52.79%-71.12%) (τ2 0.07). Mortality, treatment interruptions, defaulting and adverse events were all in line with DR-TB treatment outcomes overall. The most commonly reported adverse events were gastrointestinal disturbances and skin pigmentation. Conclusions The available evidence to date suggests that clofazimine could be considered as an additional therapeutic option in the treatment of DR-TB. The optimal dose of clofazimine and duration of use require further investigatio