Lead (Pb), mercury (Hg), and manganese (Mn) are well-known neurotoxic metals. The knowledge of toxicity was developed through an extensive amount of research, starting with lead and mercury and proceeding today with manganese. Unfortunately, the consequent implementation of preventive measures was generally delayed, causing important negative effects to the exposed populations. A review and historical reconstruction of the research development that yielded modern understanding of lead and mercury neurotoxicity was conducted to derive useful lessons for the prevention of manganese neurotoxicity. Medieval alchemists named planets and metals from gods since they were already aware of the toxicity and the adverse effects caused by lead and mercury. Historical lessons learned from these two metals may help to avoid the repetition of further mistakes regarding other neurotoxic metals like manganese. The knowledge and experience on the toxicokinetics and toxicodynamics of lead and mercury is useful and valuable to identify a proper approach to "safe" exposure levels for manganese. Further information is still needed on the early neurotoxic and neurobehavioral effects after prolonged exposure to very low doses of lead, mercury, and manganese. Nevertheless, according to the precautionary principle, effective preventive measures should be already undertaken to prevent the onset of more severe health effects in the population. This is the most important lesson to be learned and applied from more than 30 years of occupational and environmental neurotoxicology of metals. (c) 2007 Wiley-Liss, Inc.