Insulin resistance is an important "upstream" driver for reproductive and metabolic abnormalities in women with Polycystic Ovary Syndrome (PCOS). This theoretical background is now supported by substantial evidence for treating women with PCOS with insulin sensitising agents such as metformin or the thiazolidinediones. Although the available data are based upon studies comprised of relatively small numbers of patients, powerful evidence of potential benefit is emerging. Data from controlled studies, which are usually short-term and of limited magnitude, indicate modest effects of insulin sensitizers on ovulation when applied as the only drug. However, potentially important benefits are achieved when such treatment is combined with other methods. These benefits include both increased fertility and decreased risks for ovarian hyperstimulation syndrome (OHSS). Furthermore, there may also be benefits in terms of alleviation of pregnancy complications. The available evidence supports consideration of the use of metformin from the earliest stages of treatment in women with PCOS.