Next-generation sequencing (NGS) is being applied in oncology care to identify specific molecular aberrations of patient’s tumors. The use of NGS now allows for sequencing entire human genomes within a reasonable cost and practical time frames for treatment decision making. Further delineation of epigenetics, transcriptomics, metagenomics and NGS at the level of circulating tumor DNA reveal ever increasing complexity to understand these interactions and the roles they play in cancer. With the improvement in understanding the study of proteomics, it has become clear that NGS has room for innovation to someday include sequencing of proteins. Early embarkation of NGS incorporated into clinical trials has begun. Here, we review the feasibility and practicality of translating NGS from clinical trials to clinical practice.