The aetiology and pathogenesis of Parkinson's disease (PD) remain unknown. There is a consensus emerging that there are likely to be multiple aetiologies that may result in the clinical and pathological abnormalities common to the majority of patients with idiopathic PD. Genetic factors have been suggested as important in either the cause of PD or in determining susceptibility. The recent linkage in one large pedigree of a gene for autosomal dominant parkinsonism to chromosome 4q21-23 and the subsequent identification of a mutation in the alpha-synuclein gene of this region are important steps towards identifying a biochemical deficiency capable of causing selective dopaminergic cell death. However, the relevance of such a defect to the majority of patients with apparent sporadic PD remains to be established. Factors that may predispose to substantia nigral cell loss, including mitochondrial dysfunction and oxidative damage, could be common to a number of separate aetiologies. A better understanding of these and their relationship to neuronal loss may provide further clues to aetiology.