This article reviews the literature evaluating the effectiveness of various stigma reduction interventions related to mental health illnesses. An integrated search of the English language literature from 1998 to May 2008 was done using CINAHL, Medline, PubMed, Scopus, and PsychINFO databases. The results of this review emphasize that experimental clinical trials hold promise for providing evidence-based data that can be used in mental health practice. Educational and contact-based strategies used in various stigma reduction programs resulted in the most durable gains in knowledge as well as positive attitudinal and behavioral changes needed to decrease the stigma associated with mental illness. Special stigma reduction programs are to be planned for adolescent and elderly targets. Future studies have yet to be designed to identify cost-effective stigma reduction programs. Moreover, interventional studies from different cultures are encouraged. Cross-cultural interventions need to be evaluated and modified to ensure providing culturally relevant interventions.