Flucloxacillin is a common cause of drug-induced liver injury in Europe, affecting in the region of 8.5 in every 100,000 first time users of the drug. The mechanism by which the drug causes the liver injury is currently unknown but it is believed to be influenced by a combination of genetic and environmental factors. This review summarises what is currently known about the disposition of flucloxacillin in the liver, considers potential mechanisms by which flucloxacillin may cause the liver injury, and suggests candidate genes which could determine individual susceptibility to flucloxacillin-induced liver injury.