The road and rail transport sector, since the several work tipology and risk factors for workers safety and health, is an area where assessing exposure effects is very difficult. Muscoskeletal cardiovascular and neoplastic diseases are the disorders more frequently associated to professional drivers. The role of professional driving is rather well-defined in low back pain occurence, correlated to whole body vibration exposure. Professional drivers are at higher risk of ischemic cardiovascular diseases, but it is not clear whether the risk is attributable just to the occupational exposures or also to their life-style risk factors. Evidence of an excess of risk for lung, genito-urinary and hemolymphopoietic cancer is clear in the scientific literature for professional drivers. Anyway the lack in the control of confounding factors, in exposure assessment force to be very cautious in results interpretation.