The enthusiasm for nutritional supplements among athletes of any level seems inversely correlated to the real impact of these products; or at least this might be concluded after reading most systematic reviews and guidelines. Despite being frequently consumed, the supplements that have shown a positive effect on health or performance are rare. However, specific situations can require a supplementation, and this article outlines how to identify these situations and how to pick the right supplement for each condition. We also discuss the reason why providing evidence for an effect on health or performance is particularly challenging in this field.