This review provides a scientific view on how to evaluate effectively the neurotoxic potential of chemicals in order to provide adequate safeguards for human health. Detection of compounds that may cause direct, persistent, adverse effects on the nervous system should be given the most critical attention. Evaluation of the neurotoxic potential of a chemical should include descriptions of functional and morphological effects as well as the determination of the dose response, no-observed-effect level, time course and reversibility of effects. Evaluation of the nervous system in the context of standard toxicity studies that use a variety of species and study durations are appropriate screening tests (Tier 1) for the detection of potential neurotoxicity. Studies specifically designed to assess neurotoxicity (Tier 2) should be performed with chemicals for which there is an indication of neurotoxic potential and where the available data are inadequate for risk assessment. Tier 2 studies should evaluate the function and structure of the nervous system by comprehensive clinical examinations and neuropathological assessment. These studies may be conducted in conjunction with standard toxicity studies so that any potential neurotoxicity can be interpreted in the context of other systemic toxicity. More specific neurotoxicity tests (Tier 3) may be necessary for advanced characterization of discovered neurotoxicants.