Commensal microbes stimulate production of antimicrobial peptides (AMPs) by keratinocytes, sebocytes, sweat glands, and granulocytes, amplifying the innate immune defense of skin against potential pathogens. Specific microbial products also have the ability to expand certain skin lymphocyte populations. For example, riboflavin derivatives made by various bacteria are recognized by skin MAIT cells leading to their expansion and activation in the tissue. Similarly, fmet peptide produced by a particular clade of S. epidermidis is presented by nonclassical MHC-I molecules and leads to expansion of IL-17–producing CD8⁺ T cells (Tc17). DCs play a role both in initial uptake of skin bacteria and presentation of commensal antigens to naive T cells in the skin-draining lymph node as well as restimulation and cytokine production by commensal-specific skin-resident T cells. Type 2 DCs are especially capable of commensal uptake, at least for S. epidermidis, as shown in human and murine skin. In the early life window, these DC2 also play a key role in preferentially generating commensal-specific Tregs versus conventional T cells, usually Th17 cells. Commensal-specific Th17, however, also plays a key role in immune defense as well as homeostatic functions such as reepithelialization after barrier breach.