A number of different cell-based assays for cytotoxic effects of drugs exist including the lactate dehydrogenase (LDH) leakage assay, the neutral red assay, protein measurement and methyl tetrazolium (MTT) assay. We describe the development and optimization of a cell-based assay for cytotoxicity using impedance measurements. This assay is sensitive and provides reproducible results for safety pharmacology, toxicity screens of adherent, proliferating or non-proliferating cells. Changes in the impedance signal indicate effects on cell contractility, cell morphology and proliferation.