Background Acne vulgaris (acne) is the most common skin disease we see in dermatology practice. Clinically, it is characterized by a combination of open and closed comedones (formally referred to as noninflammatory lesions) and inflammatory papules and pustules. Comedonal acne is more typical in young adolescents, but can occur in combination with inflammatory papules and pustules at any time. Topical retinoids have long been advocated for the treatment of comedonal acne. Aims Given the increasing recognition of the inflammatory nature of acne and the synergistic benefits seen with fixed combinations we review the latest clinical data to provide guidance on optimal management of comedonal acne. Methods An English language literature search of Medline, EMBASE, and the Web of Science using key terms (acne, comedonal, noninflammatory, clinical trials) was conducted, and relevant articles reviewed. Results Comparative data is sparse, but we show the importance of fixed combinations with and without retinoids, where treatment benefits are comparable. Adapalene 0.1%-benzoyl peroxide 2.5% gel has been shown to be comparable to clindamycin 1%-benzoyl peroxide 5% gel, and adapalene 0.3%-benzoyl peroxide 2.5% gel. A meta-analysis suggested that clindamycin 1.2%-benzoyl peroxide 2.5% gel was more effective than clindamycin-benzoyl peroxide 5% gel in noninflammatory lesions, and two equivalent clinical programs suggest additional benefits of higher doses of benzoyl peroxide (3.75% vs 2.5%) in this fixed combination. Conclusions Clindamycin 1.2%-benzoyl peroxide 3.75% gel may afford similar benefits to adapalene 0.3%-benzoyl peroxide 2.5% gel in this sometimes difficult to treat patient population.