Microbiome based-diagnostics and microbiome-targeted therapies are novel interesting strategies in the management of skin diseases. Substantial microbiome changes have been observed in skin conditions and there seems to be significant potential to use this information in clinical diagnostics. Microbiome-targeted therapies have been studied in different settings and three main concepts have evolved. First, the cutaneous microbiome can be influenced by using methods that affect the cutaneous microbiome directly, e.g., topical pro- and prebiotics. Second, healthy or modified microbiomes or single microbial strains can be relocated onto the patients’ skin (transplantation or engraftments). And third, mechanisms that affect the cutaneous microbiome indirectly can be used, e.g., targeting the gut-skin axis (gastrointestinal probiotics). The skin microbiome remains an interesting area of research in developing new diagnostics or therapeutics in clinical medicine, especially dermatology. In addition, microbiome studies have had a great effect on our understanding of the pathophysiology of skin diseases.