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In 2007, the European Society for Human Reproduction and Embryology (ESHRE) and the American Society for Reproductive Medicine (ASRM) issued guidelines in Thessaloniki regarding the use of metformin and clomiphene for the induction of ovulation in patients with anovulatory polycystic ovary syndrome (PCOS). According to these guidelines, the use of metformin should be limited to patients with impaired glucose tolerance and should be interrupted well before the administration of clomiphene, thus restricting the use of metformin to a minority of patients with PCOS. More recent data suggest that these guidelines potentially require reconsideration. Indeed, metformin appears to be useful in patients with PCOS who have a body mass index within the normal range and present with infertility due to anovulation. Moreover, the combination of metformin with clomiphene appears to be the best treatment choice in patients with PCOS who are resistant to clomiphene, i.e. it should precede the administration of gonadotropins. In addition, the administration of metformin reduces the incidence and severity of ovarian hyperstimulation syndrome when given to patients with PCOS who undergo multiple ovulation induction for in vitro fertilization and have a high risk for this syndrome. However, it should be emphasized that more studies are needed to support the above arguments and, more importantly, to determine the factors that predict the success of ovulation induction.