Obesity is one of the main drivers of type 2 diabetes, and the increased prevalence of obesity underpins the increase in type 2 diabetes around the world. Nevertheless, there are many overweight and obese people who do not develop diabetes, and many leaner people do develop the condition. One of the reasons for this apparent discrepancy is varying genetic predisposition. Scientists have spent many years attempting to identify the DNA sequence variations and genes involved. They hoped that this work to discover genes would help them pinpoint the molecular defects that influence insulin resistance and insulin secretion, leading to new therapies, and help predict the risk for the disease. Tim Fraying provides this timely update.