During the past decade, the identification of several genes responsible for monogenic forms of Parkinson's disease has greatly increased our knowledge of the pathophysiological mechanisms of this disease. The alpha-synuclein gene, involved in very rare forms with autosomal dominant transmission, encodes a protein which is a major component of Lewy bodies, the histopathological hallmark of the disease. The Parkin gene, responsible for a significant number of cases with early onset, encodes an E3 ubiquitin-ligase, supporting the involvement of the ubiquitin-proteasome pathway in Parkinson's disease. Finally, mutations in the LRRK2 gene, which codes for a kinase with unknown substrates, accounts for a substantial fraction of autosomal dominant forms, particularly in North Africa. The study of these genes shows that the formation of Lewy bodies is not mandatory for the degeneration of dopaminergic neurons in Parkinson's disease. It remains to be determined whether the products of the genes are implicated in the same metabolic path way.