Host defense (antimicrobial) peptides, produced by all complex organisms, typically contain an abundance of positively charged and hydrophobic amino acid residues. A small synthetic peptide termed innate defense regulator (IDR‐)1018 was derived by substantial modification of the bovine neutrophil host defense peptide bactenecin. Here, we review its intriguing properties that include anti‐infective, anti‐inflammatory, wound healing, and anti‐biofilm activities. It was initially developed as an immune modulator with an ability to selectively enhance chemokine production and polarize cellular differentiation while suppressing/balancing the pro‐inflammatory response. In this regard, it has demonstrated in vivo activity in murine models including enhancement of wound healing and an ability to protect against Staphylococcus aureus, multidrug resistant Mycobacterium tuberculosis, herpes virus, and inflammatory disorders, including cerebral malaria and neuronal damage in a pre‐term birth model. More recently, IDR‐1018 was shown, in a broad‐spectrum fashion, to selectively target bacterial biofilms, which are adaptively resistant to many antibiotics and represent the most common growth state of bacteria in human infections. Furthermore, IDR‐1018 demonstrated synergy with conventional antibiotics to both prevent biofilm formation and treat pre‐existing biofilms. These data are consistent with a strong potential as an adjunctive therapy against antibiotic‐resistant infections. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd. Host defense (antimicrobial) peptides are produced by all complex organisms. A small synthetic peptide termed innate defense regulator (IDR‐)1018 was derived by substantial modification of the bovine neutrophil host defense peptide bactenecin. Here, we review its intriguing properties that include anti‐infective, anti‐inflammatory, wound healing, and anti‐biofilm activities. It was initially developed as an immune modulator and has demonstrated in vivo activity in a variety of murine models. More recently, IDR‐1018 was shown, in a broad‐spectrum manner, to selectively target bacterial biofilms, which are adaptively resistant to many antibiotics and represent the most common growth state of bacteria in human infections. Furthermore, IDR‐1018 demonstrated synergy with conventional antibiotics to both prevent biofilm formation and treat pre‐existing biofilms. This peptide, or derivatives thereof, represents a promising therapeutic agent for the treatment of antibiotic‐resistant infections.