Omega-3 polyunsaturated fatty acids (PUFAs) are essential fatty acids, derived mostly from fish oil, that have a significant anti-inflammatory effect. Data from animal studies support their role in the reproductive mechanism, and recent human studies suggest a positive effect on sperm quality and natural conception. Their general role in human fertility, and specifically in IVF treatment, however, is not clear. A few small, prospective cohort studies have examined the relationship between serum PUFAs and outcome measures and success in IVF, with conflicting results. Some have demonstrated a better chance of live birth with increased levels of serum omega-3 PUFAs, whereas others have failed to show such a correlation, and the reasons for such differences are not clear. Moreover, no well-designed, published studies have assessing whether the administration of omega-3 PUFAs before IVF treatment can improve clinical pregnancy and live birth rates. The development of safe and well-tolerated pharmaceutical forms of the active omega-3 PUFAs, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), mean that assessment of this question is now possible and future studies are warranted.