Poor drug candidate safety profiles are often identified late in the drug development process, manifesting themselves in the preclinical and clinical phases and significantly contributing to the high cost and low yield of drug discovery. As a result, new tools are needed to accelerate the assessment of drug candidate toxicity and human metabolism earlier in the drug development process, from primary drug candidate screening to lead optimization. Although high-throughput screens exist for much of the discovery phase of drug development, translating such screening techniques into platforms that can accurately mimic the human in vivo response and predict the impact of drug candidates on human toxicology has proven difficult. Nevertheless, some success has been achieved in recent years, which may ultimately yield widespread acceptance in the pharmaceutical industry.