Available for more than 5 decades, benzoyl peroxide has been a "workhorse" of acne therapy. The benefits of this agent include reduction in Propionibacterium acnes (P. acnes) with decrease in inflammatory lesions, efficacy as both "leave on" and cleanser formulations and reduced emergence of antibiotic-resistant P. acnes strains. As the effect of benzoyl peroxide on P. acnes is a direct toxic effect rather than as a "true" antibiotic, resistance to benzoyl peroxide does not occur and has never been reported. Benzoyl peroxide in hydrophase base (Brevoxyl Creamy Washes and Gels) has shown significant efficacy in the treatment of acne, with lower irritancy than other benzoyl peroxide preparations. It is felt that the low irritancy of this product is related to a unique delivery vehicle containing dimethyl isosorbide, which dissolves benzoyl peroxide crystals on the skin. Clinical studies demonstrating the efficacy and safety of benzoyl peroxide in hydrophase base will be reviewed.