Through basic science as well as animal and human clinical trials, the evidence is growing for the use of probiotics in the treatment of acne. Acne formation is dependent upon several processes, including follicular hyperkeratinization, excess sebum production, Propionibacterium acnes colonization and an inflammatory cascade. The antimicrobial properties of probiotics as well as the modification of the skin microbiome may decrease levels of P. acnes on the skin. Additionally, successful acne outcomes are influenced by compliance with topical regimens, which can commonly cause skin barrier disruption, leading to dryness and irritation. Consequently, calming inflammation as well as maintaining skin hydration and barrier repair is of primary importance when treating acne. In this chapter, we discuss how probiotics affect several factors in the pathophysiology of acne development and can improve the treatment outcomes.