Midkine (MK) shares several features in common with antibacterial proteins of the innate immune system. These include growth factor properties, heparin‐binding regions and effects on immune cells, such as recruitment and activation of neutrophils and macrophages. Indeed, recent research has demonstrated potent bactericidal and fungicidal activities of MK. This protein is constitutively expressed at relevant concentrations at barriers of the body, such as the skin and the large airways, where the body first encounters potential pathogens. The antibacterial properties of MK orthologues are preserved during evolution, as exemplified by miple2 of Drosophila. In addition to retinoic acid, promoters of MK gene expression include factors present at sites of infection, reactive oxygen species, activation of the transcription factor NF‐κB and hypoxia. In the light of the development of resistance in pathogenic bacteria to conventional antibiotics, MK is an interesting molecule that could serve as a template in developing novel therapeutic strategies against bacterial and fungal infections, either alone or in combination with conventional antibiotics.Linked ArticlesThis article is part of a themed section on Midkine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue‐4