ABSTRACT As phenotypic screening makes a comeback in drug discovery, its major issue is drug target identification. There aren’t good generalizable approaches to do target identification for compounds of interest. Identifying how a new drug works at the molecular level is critical for improving it, which is often needed to give it the best chance of ultimately being both safe and effective in patients. In this proposal, we demonstrate a genome-wide CRISPRi/a screening process in human cells that readily identifies the molecular target(s) for drugs of interest. We present preliminary evidence it can also identify alternative targets for the disease indication for the drug as well as potential side effect targets. We demonstrate this screening process can be applied to drugs for diverse diseases. Thus, it has the potential to improve the number of drugs that make it through drug development pipelines that currently have high failure rates such as those for Alzheimer’s and diabetes. In the last two decades companies like Foundation Medicine have used genomics to make an increasing impact on disease diagnostics in the Healthcare industry. We propose to similarly use genomics to make an impact on the pharmaceutical industry creating a “drug diagnostics” market in the process.