Recent advances in genome technologies and the ensuing outpouring of genomic information related to cancer have accelerated the convergence of discovery science and clinical medicine. Successful examples of translating cancer genomics into therapeutics and diagnostics reinforce its potential to make possible personalized cancer medicine. However, the bottlenecks along the path of converting a genome discovery into a tangible clinical endpoint are numerous and formidable. In this Perspective, we emphasize the importance of establishing the biological relevance of a cancer genomic discovery in realizing its clinical potential and discuss some of the major obstacles to moving from the bench to the bedside.