The National Cancer Institute has set the goal of eliminating suffering and death due to cancer by 2015. A key strategy to achieve this goal is to improve early detection and prevention using novel molecularly targeted cancer diagnostics and therapeutics. As we begin to better understand the cellular and molecular pathways of carcinogenesis, it is possible to identify and treat precursors to cancer before changes are detected at anatomical levels. Developing imaging techniques with the ability to detect molecular signatures will not only target these abnormalities for therapy at the earliest possible stages but will also prove useful in further unraveling the molecular origins of cancer. The ability to image noninvasively in real-time makes optical imaging well suited to early detection. Molecular characterization in combination with optical imaging provides a sensitive and specific method to detect and prevent the progression of precancerous lesions.