The Cancer Cell Line Encyclopedia (CCLE) is a comprehensive resource that compiles gene expression, chromosomal copy number, and massively parallel sequencing data from 947 human cancer cell lines. Coupled with pharmacologic profiles for 24 anticancer drugs across 479 lines, the CCLE enables the identification of genetic, lineage, and gene expression-based predictors of drug sensitivity. Key findings include the correlation of plasma cell lineage with sensitivity to IGF1 receptor inhibitors, *AHR* expression with MEK inhibitor efficacy in *NRAS*-mutant lines, and *SLFN11* expression predicting sensitivity to topoisomerase inhibitors. These results suggest that large, annotated cell line collections can aid in preclinical stratification of anticancer agents, potentially speeding the development of personalized therapeutic regimens. The CCLE provides a robust platform for future studies to enhance our understanding of cancer biology and drug discovery.The Cancer Cell Line Encyclopedia (CCLE) is a comprehensive resource that compiles gene expression, chromosomal copy number, and massively parallel sequencing data from 947 human cancer cell lines. Coupled with pharmacologic profiles for 24 anticancer drugs across 479 lines, the CCLE enables the identification of genetic, lineage, and gene expression-based predictors of drug sensitivity. Key findings include the correlation of plasma cell lineage with sensitivity to IGF1 receptor inhibitors, *AHR* expression with MEK inhibitor efficacy in *NRAS*-mutant lines, and *SLFN11* expression predicting sensitivity to topoisomerase inhibitors. These results suggest that large, annotated cell line collections can aid in preclinical stratification of anticancer agents, potentially speeding the development of personalized therapeutic regimens. The CCLE provides a robust platform for future studies to enhance our understanding of cancer biology and drug discovery.