Parkinson's disease is characterized by a triad of cardinal motor symptoms (bradykinesia, rigidity and tremor) resulting from the loss of dopaminergic neurons in the substantia nigra. This synucleinopathy is classified in the larger group of Lewy body disorders. Currently, these symptoms are relatively well alleviated by drugs that restore dopaminergic neurotransmission, andlor by deep brain stimulation. It is not yet possible to halt the underlying degeneration, or to treat symptoms due to non-dopaminergic neuron damage. This review examines the mechanisms of neuronal degeneration in Parkinson's disease, new targets for neuroprotection, and the mechanisms causing symptoms resistant to current treatments.