Case-control studies have many advantages for identifying disease-related genes, but are limited in their ability to detect gene-environment interactions. The prospective cohort design provides a valuable complement to case-control studies. Although it has disadvantages in duration and cost, it has important strengths in characterizing exposures and risk factors before disease onset, which reduces important biases that are common in case-control studies. This and other strengths of prospective cohort studies make them invaluable for understanding gene-environment interactions in complex human disease.