As human skin hosts a diverse microbiota in health and disease, there is an emerging consensus that dysregulated interactions between host and microbiome may contribute to chronic inflammatory disease of the skin. Neonatal skin is a unique habitat, structurally similar to the adult but with a different profile of metabolic substrates, environmental stressors, and immune activity. The surface is colonized within moments of birth with a bias toward maternal strains. Initial colonists are outcompeted as environmental exposures increase and host skin matures. Nonetheless, early life microbial acquisitions may have long-lasting effects on health through modulation of host immunity and competitive interactions between bacteria. Microbial ecology and its influence on health have been of interest to dermatologists for >50 years, and an explosion of recent interest in the microbiome has prompted ongoing investigations of several microbial therapeutics for dermatological disease. In this review, we consider how recent insight into the host and microbial factors driving development of the skin microbiome in early life offers new opportunities for therapeutic intervention. IMPACT: Advancement in understanding molecular mechanisms of bacterial competition opens new avenues of investigation into dermatological disease. Primary development of the skin microbiome is determined by immunological features of the cutaneous habitat. Understanding coordinated microbial and immunological development in the pediatric patient requires a multidisciplinary synthesis of primary literature.