Alitretinoin is a retinoid receptor pan-agonist, which has been investigated in the treatment of Kaposi's sarcoma (KS). Binding with high affinity to all known retinoid receptors, alitretinoin is thought to regulate proliferation, differentiation, and apoptosis of KS cells. Significantly more patients experienced complete or partial responses [according to the AIDS Clinical Trials Group (ACTG) criteria for topical treatment of cutaneous KS] with alitretinoin 0.1% gel 2 to 4 times daily than with vehicle gel in 2 phase III, multicenter, 12-week, randomized, double-blind clinical trials of patients with AIDS-related KS (35 vs 18%, p = 0.002 and 37 vs 7%, p = 0.00003, respectively). Responses were also observed in patients refractory to prior systemic or topical anti-KS therapies. In an intent-to-treat analysis in a phase II trial, 37% of patients with AIDS-related KS receiving alitretinoin capsules 60 to 100 mg/m2/day demonstrated either complete or partial responses (determined by ACTG criteria). The majority of adverse events associated with alitretinoin 0.1% gel were classified as either mild or moderate, occurred at the site of application and were reversible. In both phase III trials, rash was the most common adverse event. The most common adverse events in patients taking alitretinoin capsules included headache, dry skin, rash, alopecia, exfoliative dermatitis, and hyperlipidemia.