Parkinson's disease (PD) is characterized clinically by rest tremor, rigidity, bradykinesia and pathologically by degeneration of nigrostriatal dopamine neurons. Motor fluctuations (wearing off) and motor complications (dyskinesia) are common features of the long-term treatment of PD. Ongoing clinical and preclinical research has led to the discovery of promising new therapeutic targets that might prevent or reduce motor complications. Newer approaches modulating non-dopaminergic systems including adenosine A2A antagonists, monoamine oxidase-B inhibitors, glutamatergic antagonists, adrenergic receptor antagonists and serotonergic agents are encouraging strategies for management of advanced PD. Recent developments in levodopa delivery formulations include duodenal infusion of a levodopa/carbidopa, new extended-release levodopa and oral pro-levodopa forms. Recent clinical trials revealed diverse but promising results raising the possibility of new therapeutic modalities for PD in the near future.