During the past 15 years, genomic analysis for selection of molecularly guided targeted therapy has become standard of care for a wide range of advanced solid tumors including non–small cell lung cancer (NSCLC) (eg, EGFR, ALK, ROS1), colorectal cancer (eg, KRAS, BRAF), breast cancer (eg, PIK3CA), and urothelial carcinoma (eg, FGFR2/3), with emerging targets being studied across a range of cancers. This has led to a growing array of available targeted therapies and a parallel increase in the number and diversity of molecular diagnostic tests to help with treatment selection. Tumor sequencing not only helps to inform which treatments are likely to be effective but also point to which therapies should not be used (eg, EGFR antibodies in KRAS-mutant colon cancer, immune checkpoint inhibitors in EGFR or ALK-positive NSCLC).