Our research group focuses on the synthesis of bioactive natural products and peptides as potential therapeutic agents. This lecture will highlight the development of peptidomimetics for the treatment of neurogenetic diseases and the synthesis of antimicrobial peptides to combat infectious disease. We also demonstrate the use of the thiol-ene reaction as an expedient method to chemoselectively lipidate a cysteine residue within a polypeptide. Application of this patented CLipPA (Cys Lipidation on a Peptide or Amino acid) technology to the synthesis of novel lipopeptides as self-adjuvanting cancer vaccines, antimicrobial peptides, peptide hormones and peptide-based biomaterials will be illustrated. Our use of a thiol-ene reaction to expand the repertoire of methods to effect peptide stapling and bioconjugation will also be presented.