One out of four deaths in the USA is due to cancer. Identification of populations at risk of developing cancer is important as it provides opportunities for prevention and treatment of cancer. Biomarkers are measurable indicators of exposure effects and susceptibility or disease state, and are used to understand the mechanisms of cancer progression. In recent molecular epidemiology studies genomic, proteomic, and epigenomic markers have been utilized which exhibit high sensitivity and specificity for different tumor types and can be assayed in biofluids and other specimens collected by non-invasive technologies. The current challenges and future directions in the field are discussed in this article.