Patients with diabetes differ in how their diabetes responds to treatment. Some individuals can have a marked glycaemic response; others have a poor response. Some have adverse drug reactions (e.g. hypoglycaemia with sulphonylureas, or diarrhoea with metformin), others do not. Diabetes is one of the few disease areas (outside of cancer therapy) where pharmacogenetics is impacting on our understanding of drug mechanism, and on direct clinical care. In this review, we address the complexities of studying drug response in diabetes, and highlight key recent advances both within monogenic diabetes and common type 2 diabetes.