Antimicrobial peptides represent promising therapeutic agents against bacterial and fungal pathogens. Efforts to improve peptide activity through structure/function studies have been numerous but they have not traditionally used the bioinorganic chemistry toolbox. Nature exploits inorganic chemistry to design antimicrobial peptides in three ways: (1) the use of metal ions as structural cofactors; (2) removal of metal ions through chelation; and (3) generation of reactive oxygen species (ROS). This article reviews some of the findings of the antimicrobial community that highlight the role of transition metal ions.