Midkine (MK) is a pleiotropic growth factor prominently expressed during embryogenesis but down‐regulated to neglible levels in healthy adults. Many published studies have demonstrated striking MK overexpression compared with healthy controls in various pathologies, including ischaemia, inflammation, autoimmunity and, most notably, in many cancers. MK expression is detectable in biopsies of diseased, but not healthy, tissues. Significantly, because it is a soluble cytokine, elevated MK is readily apparent in the blood and other body fluids such as urine and CSF, making MK a relatively convenient, accessible, non‐invasive and inexpensive biomarker for population screening and early disease detection. The first diagnostic tests that quantify MK are just now receiving regulatory clearance and entering the clinic. This review examines the current state of knowledge pertaining to MK as a biomarker and highlights promising indications and clinical settings where measuring MK could make a difference to patient treatment. I also raise outstanding questions about reported variants of MK as well as MK's bio‐distribution in vivo. Answering these questions in future studies will enhance our understanding of the significance of measured MK levels in both patients and healthy subjects, and may reveal further opportunities for measuring MK to diagnose disease. MK has already proven to be a biomarker that can significantly improve detection, management and treatment of cancer, and there is significant promise for developing further MK‐based diagnostics in the future.Linked ArticleThis article is part of a recent themed section on Midkine, published in volume 171 issue 4. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue‐4