In the United States, the regulation and testing of chemicals that may impact on human health is mandated by a number of different laws and regulated by several government agencies. Toxicologic screening in laboratory animals has created a major database for predicting adverse health effects of drugs, food and cosmetic ingredients, and manufactured chemicals. Test protocols and reporting requirements frequently differ between government agencies within the United States and between nations. Until recently, the emphasis for this required testing has been to identify those chemicals that may result in cancer or birth defects with little or no emphasis placed on neurobehavioral testing. The so-called “traditional toxicologic screen” presently includes acute, subchronic, chronic, teratology, and reproductive multispecies testing. The report for each segment of the test screen contains a myriad of data elements that have been observed by numerous technicians in the testing laboratory. These laboratory tests vary from general animal observations of animal body weight and food consumption to tests for hematology, blood chemistry, urinalysis, and histopathology. In addition, specialized tests may include other physiological measurements, neurologic tests, eye exams as well as functional testing to evaluate performance (e.g., open field, swimming maze, and T-maze). Reliability, quality control, and the difficulty in converting technician observation into quantifiable data elements that are free from bias is a primary concern for all testing laboratories. This paper focuses on the neurotoxicologic and behavioral information that can be gleaned from traditional toxicologic screens, the collection of study data, the effect of model selection, and the environmental considerations that may affect study outcome. The paper includes examples of compounds previously reported in the literature.