Diet has major effects on human health. In this special issue of Science, "Diet and Health," four Reviews explore the connections between what we eat and our well-being, as well as the continuing controversies in this space. Among topics explored: How much fat we should eat? Recommendations have swung from one extreme to the other. In a Review by nutrition scientists with widely varying perspectives, David S. Ludwig and colleagues highlight broad consensus emerging regarding what the proportion of fat should be in a healthy diet, and, importantly, which particular fats seem to be the most healthful. A second Review by Christopher Gentile and Tiffany Weir touches on a promising and emerging area of investigation - how diet influences our give-and-take interaction with the symbionts in our gut. In a third Review, Andrea Di Francesco and colleagues overview the power of adjusting meal size and meal frequency; it's not just what you eat, but when you eat it, and periods of fasting have some remarkable health benefits, they say. In a final Review, Louise M. Burke and John A. Hawley dissect nutritional approaches to optimal performance in elite athletes. There is not a single, superior "athletic diet," they say. Rather, different sports - with different training regimens and metabolic demands - have led to a diversity in sports nutrition practices between athletes. A theme throughout this special issue is that much of the disagreement on what we should eat reflects a lack of solid scientific studies on humans; additional well-designed studies are needed to resolve what's the best diet for people, and how that varies with activity at different life stages and for different individuals.