Behavioral toxicology is an important discipline of toxicology that traces its roots back to the origin of psychology. A parallel development can be traced for behavioral toxicology and psychology, in that both were focused on the mind or behavior, as distinct from neurology, that recognized the brain as the ultimate target. Ancient physicians and non-medical authors incidentally described the effects of neurotoxic agents on mood. In the last two centuries, experimental psychology, behaviorism and behavioral pharmacology further developed the observation of behavior with scientific methodology. During the Industrial Revolution exposure to neurotoxicants became widespread in the western world and the consequent “psycho-organic syndrome” was likely to affect a large part of the working population. Occupational Medicine met behavioral toxicology in the 1960s. The assessment of the effects of exposure on behavior was achieved with specific tests for motor and cognitive functions, and computer technology could be used to control and analyze behavioral experiments. The contribution of this discipline became further important in the identification of early adverse effects, also from environmental and dietary exposure. The detection of behavioral changes can precede the detection of neural changes, which makes the assessment of behavior especially suitable for risk assessment. Neurobehavioral methodology has further developed in the latest years towards a global and integrated approach to the different life stages of individuals, from early life to old age.