Molecular epidemiology was introduced in the study of cancer in the early 1980s, with the expectation that it would help overcome some important limitations of epidemiology and facilitate cancer prevention. The first generation of biomarkers has indeed contributed to our understanding of mechanisms, risk and susceptibility as they relate largely to genotoxic carcinogens, resulting in interventions and policy changes to reduce risk from several important environmental carcinogens. New and promising biomarkers are now becoming available for epidemiological studies, including alterations in gene methylation and gene expression, proteomics and metabolomics. However, most of these newer biomarkers have not been adequately validated, and their role in the causal paradigm is not clear. Systematic validation of these newer biomarkers is urgently needed and can take advantage of the principles and criteria established over the past several decades from experience with the first generation of biomarkers. Prevention of only 20% of cancers in the United States alone would result in 300 000 fewer new cases annually, avoidance of incalculable suffering, and a savings in direct financial costs of over US$20 billion each year (1). Molecular epidemiology can play a valuable role in achieving this goal.