Large-scale genomics studies are transforming our understanding of tumor biology; however, despite a dramatic increase in available data, translating genomic findings to clinical practice remains a significant challenge. This session will focus on current efforts to leverage genomic data to advance clinical radiation oncology. Presentations will describe preclinical systems used in genomic analyses and will explain the biological and technical underpinnings of common genomic assays. All speakers are active translational investigators and will highlight different genomic platforms in current use, including DNA-based mutational and copy-number analyses, RNA-based gene expression analyses, and metabolic/proteomic approaches. We will examine several representative biomarkers in detail to highlight the path from biomarker discovery to clinical implementation. Finally, we will describe the challenges that exist when attempting to validate tumor genomic features as prognostic and/or predictive biomarkers, and we will highlight what we see as opportunities for on-going investigations that are unique to radiation oncology.