Epidemiological studies show that smoking is associated with a lower incidence of Parkinson's disease (PD). This finding is important because it could provide clues about therapeutic strategies for protection against this debilitating movement disorder. Smoke contains numerous chemicals that could be responsible for the apparent protective effect. Here, a role for nicotine is considered, because this chemical stimulates brain dopaminergic systems and provides some symptomatic benefit in PD. Nicotine also has a neuroprotective action. Putative factors and signaling pathways involved in the actions of nicotine are discussed. An understanding of the molecular basis for the reduced occurrence of PD in tobacco users is crucial for the development of intervention strategies to reduce or halt disease progression.