Both comedogenesis and the development of inflammatory lesions in acne vulgaris appear to be related to genetic as well as immune processes. The key regulatory cytokine, interleukin-1alpha, has recently been documented as playing a major role in both the hypercornification and the orchestration of immune factors, ultimately resulting in noninflammatory and inflammatory lesions. Topical retinoids, such as tretinoin, and topical retinoid analogs, such as adapalene and tazarotene, help normalize the abnormal follicular keratinocyte desquamation - a key pathophysiologic factor in comedogenesis. This normalization also helps mitigate against the development of a propitious microenvironment for Propionibacterium acnes. Preclinical data suggest that topical retinoids and retinoid analogs may also have direct anti-inflammatory effects. A wealth of clinical data confirms that topical retinoids and retinoid analogs significantly reduce inflammatory lesions. Comparative clinical trials also demonstrate that adapalene has the best cutaneous tolerability profile of all these agents. Optimal therapy for inflammatory acne would involve the use of topical retinoids or retinoid analogs combined with oral or topical antibacterials.