Combination therapy of acne vulgaris is often more effective than monotherapy, but understanding the limitations and risks of such therapy is essential to maximize safety and efficacy. A recent study revealed that 7% of patients using topical dapsone gel, 5%, in combination with benzoyl peroxide developed temporary skin discoloration. Dubina and Fleischer further investigate the interactions between topical dapsone gel, sulfacetamide sodium lotion, benzoyl peroxide, clindamycin phosphate, and retinoids. Their data reveal that benzoyl peroxide products produce an orange-brown discoloration when mixed with either sulfacetamide or dapsone. Even dapsone alone imparted a slight color. These data may be used by dermatologists to develop combination treatment plans that avoid combining these ingredients in a manner that would lead to discoloration.