Background Treatment guidelines are lacking for classic Kaposi sarcoma. Objective We sought to review the evidence on efficacy of treatments for classic Kaposi sarcoma. Methods Articles published in English or French in MEDLINE, Trip, Cochrane Library, and Pascal databases from 1980 to December 2010 were screened. Studies reporting at least 5 patients treated for histologically confirmed classic Kaposi sarcoma were selected. Primary outcome was a decrease in the number or size of lesions or of lymphedema. We reviewed 26 articles matching the inclusion criteria for methodologic quality, classifying them according to World Health Organization criteria. Results The percentage of patients with a 50% or greater decrease in lesions was 71% to 100% for pegylated liposomal doxorubicin, 58% to 90% for vinca-alkaloids, 74% to 76% for etoposide, 93% to 100% for taxanes, 100% for gemcitabine, 97% for the combination of vinblastine and bleomycin, 71% to 100% for interferon alfa-2, 43% for thalidomide, and 12% for indinavir. For local treatments, a decrease of 50% or greater was achieved in 62% of lesions for intralesional vincristine, 50% to 90% for intralesional interferon alfa-2, 56% for imiquimod, and 25% for nicotine patches. A complete response was attained in 60% to 93% of lesions with radiotherapy. Limitations Eligible trials were of poor quality. The lack of standardized classification of disease activity and clinical outcomes precluded the comparison of studies. Conclusion The evidence for efficacy of any particular intervention is of low quality and does not support recommending any particular therapeutic strategy. Further studies are required and it will be important to standardize the assessment of disease activity and clinical response.