The topical retinoid tretinoin and topical retinoid analogues such as adapalene and tazarotene help normalize hyperkeratinization in acne vulgaris and have demonstrated significant anti-inflammatory effects in experimental trials. Inhibition of various immune factors, including the activity of leukocytes, the release of proinflammatory cytokines and other mediators, and the expression of transcription factors and toll receptors involved in immunomodulation, has emerged in both in vitro studies and in vivo animal experiments. These multiple mechanisms of action should encourage clinicians to consider these agents in the first-line management of inflammatory acne lesions.