Trillions of bacteria, fungi, viruses, archaea, and small arthropods colonize the skin surface, collectively comprising the skin microbiome. Generations of researchers have classified these microbes as transient versus resident, beneficial versus pathogenic, and collaborators versus adversaries. Culturing and direct sequencing of microbial inhabitants identified distinct populations present at skin surface sites. Herein, we explore the history of this field, describe findings from the current molecular sequencing era, and consider the future of investigating how microbes and antimicrobial therapy contribute to human health.