Levodopa is the gold standard for the symptomatic treatment of Parkinson's disease (PD). However, chronic treatment is associated with development of motor complications in the majority of patients. Recent laboratory studies suggest that pulsatile administration of a short-acting agent, such as levodopa, contributes to the development of these problems and that they might be mitigated through the use of longer-acting dopamine agonists. Placebo-controlled clinical trials have shown that dopamine agonists have anti-parkinsonian effects in patients with early PD. More importantly, four different prospective double-blind studies have demonstrated that initiating symptomatic therapy with a dopamine agonist is associated with a significantly reduced risk for development of motor complications than is initial treatment with a dopamine agonist. Furthermore, several lines of laboratory research suggest that dopamine agonists might protect dopaminergic neurons in PD and retard the rate of disease progression. Double-blind trials using clinical and imaging end points are now testing this hypothesis and the results should soon be available. On the basis of this evidence, a rational approach to the treatment of PD patients who are not elderly or cognitively impaired is to initiate therapy with a dopamine agonist and supplement with levodopa when dopamine agonist monotherapy can no longer provide satisfactory clinical control.