The latest advances in the research of the effect of skin microbiome on the occurrence of acne raised the need for the development of new effective treatments for the long-term use in persistent or recurrent disease. The review presents an analysis of foreign and domestic studies on the issues of pathogenesis and treatment of acne. The latest data on the role of skin microbiome imbalance in the occurrence of acne are presented. The Cutibacterium acnes phylotypes diversity loss acts as a trigger for innate immunity activation and chronic inflammation in acne. We show the main directions in the treatment of acne based on international and Russian clinical guidelines. Today, a new solution in acne therapy lies in a multimodal approach to the impact on various links in the pathogenesis of acne to increase therapeutic efficacy, safety, and patient adherence to therapy. The place of topical fixed-dose combination drugs in the treatment of mild to moderate acne has been determined. Due to the growing resistance to antibiotics and their more limited use, it was observed that there is a need to develop new effective treatments for the long-term use. The studies showed that the fixed combination of adapalene/metronidazole is a highly effective treatment for moderate to moderately severe papulopustular acne. The comparative analysis of the use of fixed-dose combinations of adapalene/metronidazole and adapalene/clindamycin in the treatment of patients with acne revealed the comparable efficacy and good tolerability of both combinations. The findings of foreign and domestic studies have proved that the adapalene/metronidazole combination is an effective and safe drug to treat mild to moderate acne.