Natural cationic host defence (antimicrobial) peptides are widely distributed gene encoded molecules with diverse structures. There are more than 1200 natural Host Defence Peptides (HDPs) described to date. Due to the multifunctional roles defined for such peptides there is a keen interest in the potential therapeutic applications of HDPs and their synthetic mimics, Antimicrobial peptides and Innate Defence Regulator (IDR) peptides. These peptides constitute two broad classes of potential therapeutics; (i) with direct antimicrobial and/or anti-biofilm activity, and (ii) with immune-modulating and/or anti-inflammatory activity. Exploiting the immunomodulatory functions of these peptides represents a new therapeutic approach for resolution of infections and inflammatory disorders.