Polycystic ovary syndrome (PCOS) is a heterogeneous clinical condition. In most women, especially in the obese, all features of the metabolic syndrome, particularly insulin resistance and associated hyperinsulinaemia, are present. Insulin is a physiological hormone regulating ovarian function, specifically ovarian steroidogenesis and androgen blood transport and/or activity in the target tissues. Hyperinsulinaemia may therefore play a pivotal role in favouring the hyperandrogenic state and related clinical and metabolic alterations. The abdominal obesity phenotype is common, affecting more than half of PCOS women. Menstrual cycles and fertility rate are negatively affected by the presence of insulin resistance, hyperinsulinaemia and obesity. PCOS women with obesity and insulin resistance are the obvious target for lifestyle intervention, such as changes in dietary habits and increased physical activity. Weight loss should therefore represent the first-line approach in the treatment of obese PCOS women, since it significantly improves hormonal and metabolic abnormalities and may favour spontaneous ovulation and improve fertility rate in the majority of patients. Individualized pharmacological support aimed at favouring weight loss and maintenance and improving insulin resistance may play a complementary role to lifestyle intervention.