The human skin microbiota forms a key barrier against skin pathogens and is important in modulating immune responses. Recent studies identify lactobacilli as endogenous inhabitants of healthy skin, while inflammatory skin conditions are often associated with a disturbed skin microbiome. Consequently, lactobacilli-based probiotics are explored as a novel treatment of inflammatory skin conditions through their topical skin application. This review focuses on the potential beneficial role of lactobacilli (family Lactobacillaceae ) in the skin habitat, where they can exert multifactorial local mechanisms of action against pathogens and inflammation. On one hand, lactobacilli have been shown to directly compete with skin pathogens through adhesion inhibition, production of antimicrobial metabolites, and by influencing pathogen metabolism. The competitive anti-pathogenic action of lactobacilli has already been described mechanistically for common different skin pathogens, such as Staphylococcus aureus , Cutibacterium acnes , and Candida albicans . On the other hand, lactobacilli also have an immunomodulatory capacity associated with a reduction in excessive skin inflammation. Their influence on the immune system is mediated by bacterial metabolites and cell wall-associated or excreted microbe-associated molecular patterns (MAMPs). In addition, lactobacilli can also enhance the skin barrier function, which is often disrupted as a result of infection or in inflammatory skin diseases. Some clinical trials have already translated these mechanistic insights into beneficial clinical outcomes, showing that topically applied lactobacilli can temporarily colonize the skin and promote skin health, but more and larger clinical trials are required to generate in vivo mechanistic insights and in-depth skin microbiome analysis.