The human skin microbiome, composed of bacteria, fungi, and viruses, plays a crucial role in protecting the body from pathogens and educating the immune system. Despite the harsh conditions of the skin, such as dryness, acidity, and nutrient scarcity, a diverse community of microorganisms colonizes the skin. This review discusses the use of amplicon and shotgun metagenomic sequencing to study the taxonomic diversity of skin-associated microorganisms, focusing on the composition of microbial communities in health and disease, and the interactions between these communities and the immune system. Key findings include: - The skin microbiome is highly dependent on the physiological characteristics of the skin site, with different microbial communities found in sebaceous, moist, and dry areas. - Bacteria are the most abundant kingdom across sites, while fungi are less abundant. Eukaryotic DNA viruses show individual-specific colonization patterns. - Longitudinal studies reveal that skin microbial communities are largely stable over time, with stability maintained by the maintenance of strains rather than reacquisition of species from the environment. - The skin microbiome is influenced by factors such as age, with changes during puberty leading to a shift in microbial composition. - Interactions between microorganisms, such as competition and synergy, play a significant role in community assembly and stability. - Common skin diseases like acne, atopic dermatitis, and chronic wounds are associated with dysbiosis, where the balance of the microbial community is disrupted. - The immune system and skin microbiota interact closely, with microorganisms educating the immune system and influencing immune responses to pathogens. The review highlights the importance of understanding the skin microbiome in health and disease, and the potential for developing therapeutic strategies based on this knowledge.The human skin microbiome, composed of bacteria, fungi, and viruses, plays a crucial role in protecting the body from pathogens and educating the immune system. Despite the harsh conditions of the skin, such as dryness, acidity, and nutrient scarcity, a diverse community of microorganisms colonizes the skin. This review discusses the use of amplicon and shotgun metagenomic sequencing to study the taxonomic diversity of skin-associated microorganisms, focusing on the composition of microbial communities in health and disease, and the interactions between these communities and the immune system. Key findings include: - The skin microbiome is highly dependent on the physiological characteristics of the skin site, with different microbial communities found in sebaceous, moist, and dry areas. - Bacteria are the most abundant kingdom across sites, while fungi are less abundant. Eukaryotic DNA viruses show individual-specific colonization patterns. - Longitudinal studies reveal that skin microbial communities are largely stable over time, with stability maintained by the maintenance of strains rather than reacquisition of species from the environment. - The skin microbiome is influenced by factors such as age, with changes during puberty leading to a shift in microbial composition. - Interactions between microorganisms, such as competition and synergy, play a significant role in community assembly and stability. - Common skin diseases like acne, atopic dermatitis, and chronic wounds are associated with dysbiosis, where the balance of the microbial community is disrupted. - The immune system and skin microbiota interact closely, with microorganisms educating the immune system and influencing immune responses to pathogens. The review highlights the importance of understanding the skin microbiome in health and disease, and the potential for developing therapeutic strategies based on this knowledge.