Fueled by the complete genomic data acquired from the human genome project and the desperate clinical need of comprehensive analytical tools to study a heterogeneous disease like cancer, genomic and proteomic technologies have evolved rapidly, accelerating the rate and number of discoveries in clinical cancer research. These discoveries include mechanistic understanding of cancer biology as well as the identification of biomarkers supporting early detection, molecular classification of tumors, molecular predictors of metastasis, treatment response, and prognosis. While the technical advances have been significant, clinical researchers and practicing physicians are now confronted with the challenges of understanding technically and statistically complex data sets, translating this complex information to fit clinical contexts and incorporating it into clinical studies. In this review, we will summarize the available technologies and associated bioinformatics, discuss studies that are clinically relevant, and discuss the limitations we are still facing. We will present a framework for future directions of these technologies and how we believe they should be applied in clinical studies.