This literature review indicates that professional drivers have excess cardiac risk that is not fully explained by standard risk factors. The contribution of occupation is suggested by two independent methods and by psychophysiological studies during on the job driving. Driving has been conceptualized as a threat-avoidance task. Stimuli encountered in traffic are not inherently aversive but become so by association with driving experience, a formulation corroborated by laboratory studies in which stimuli such as car headlights elicit cardiovascular hyperreactivity and electroencephalographic signs of arousal in professional drivers. More-advanced neurophysiological methods (event-related potentials) show higher cortical electronegativity to imperative signals among professional drivers than among non-driver referents. These data are viewed in light of reports of possible associations between event-related slow potentials and cardiac risk. A clinically and ecologically relevant neurocardiological model is proposed, and preventive strategies, including workplace interventions, are suggested.