The focus of this review is the expression, regulation, assembly and function of neurofilaments and their relationship to neurodegenerative diseases. In the mammalian nervous system the three neurofilament genes are expressed exclusively in differentiated central or peripheral neurones. They are necessary to maintain the highly polarised neuronal cell shape. The three proteins are assembled in intermediate filaments as obligate heteropolymers. Their expression is precisely regulated during development and during adult life, according to the neuronal cell type and its physiological state. At the transcriptional level, temporal and cell specific expression in neurones is driven by elements located both in the 5’ upstream region and within the gene itself. Further, posttranscriptional/posttranslational modifications are involved in the selective and differentiated expression of neurofilaments. The latter are probably also involved in variable neurofilament levels and turnover found in different neuronal subtypes. In numerous neurodegenerative diseases, neurofilaments accumulate in the axons and the perikaria. A large body of evidence shows that overexpression and mutations of the neuronal intermediate filament proteins can lead directly to neuronal degeneration. Studies of various hereditary progressive paralysis in mammals strongly sustain the knowledge that neurofilament abnormalities can be responsible for some neurodegenerative and motoneurone disease.