The dramatic increase in the prevalence of obesity coincides with a decline in reproductive health indices in both sexes. Energy excess mediates changes to the regulatory mechanisms of the reproductive system. Obese individuals exhibit increased estrogen concentrations, due to the overexpression of aromatase in the adipose tissue; via a negative feedback loop, men present with symptoms of hypogonadotropic hypogonadism. These hormonal changes, along with increased oxidative stress, lipotoxicity and disturbances in the concentrations of adipokines, directly affect the gonads, peripheral reproductive organs and the embryo. Clinical evidence is somewhat contradicting, with only some studies advocating worse semen parameters, increased incidence of erectile dysfunction, increased doses of ovulation induction medications, and worse live birth rates in assisted reproductive technology (ART) cycles in obese individuals compared with those of normal weight. Similar conclusions are drawn about patients with insulin resistance syndromes, namely polycystic ovary syndrome (PCOS). As far as treatment options are concerned, lifestyle changes, medical therapy and bariatric surgery may improve the reproductive outcome, although the evidence remains inconclusive. In this review, we summarize the evidence on the association of obesity and reproductive health on both the molecular and the clinical level, and the effect of weight-loss interventions on reproductive potential.