Antimicrobial peptides (AMPs) are small molecular weight proteins with broad spectrum antimicrobial activity against bacteria, viruses, and fungi. These evolutionarily conserved peptides are usually positively charged and have both a hydrophobic and hydrophilic side that enables the molecule to be soluble in aqueous environments yet also enter lipid-rich membranes. Once in a target microbial membrane, the peptide kills target cells through diverse mechanisms. Cathelicidins and defensins are major groups of epidermal AMPs. Decreased levels of these peptides have been noted for patients with atopic dermatitis and Kostmann's syndrome, a congenital neutropenia. In addition to important antimicrobial properties, growing evidence indicates that AMPs alter the host immune response through receptor-dependent interactions. AMPs have been shown to be important in such diverse functions as angiogenesis, wound healing, and chemotaxis. As our knowledge of AMP biology expands, the precise role and relevance of these peptides will be better elucidated.