Both insulin resistance and dyslipidaemia are determined by genetic and environmental factors. Depending on their expression and their function, gene variants may influence either insulin action or dyslipidaemia. The purpose of this review was to give some examples from recent studies of gene variants that influence insulin signalling and the interaction between gene and diet to predispose insulin resistance. Recent findings indicate a major role for genetic susceptibility to the insulin resistance syndrome. Nutrition also plays an important role in the development and progression of the condition. Genetic background may interact with habitual dietary fat composition, affecting predisposition to the insulin resistance syndrome and individual responsiveness to changes in dietary fat intake. Due to the complex nature of gene–environment interactions, therefore, therapeutic dietary therapy may require a ‘personalized’ nutrition approach in the future. Although results have not always been consistent, gene variants that affect primary insulin action or dyslipidaemia, and particularly their interaction with the environment, are important modulators of glucose metabolism and insulin resistance syndrome.