Neurofilaments are the most abundant class of intermediate size filaments in adult neurons in central and peripheral nervous system. For a long time, neurofilaments have been thought to be implied in neurodegenerative diseases like lateral amyotrophic sclerosis or infantile spinal muscular atrophy. More recently, it has been observed that retinal ganglion cells containing highest levels of neurofilament protein were the most susceptible to cell death in experimental glaucoma. Currently, it has been shown that usually, in neurodegenerative diseases, a failure in the assembly of neurofilaments and neurofilament accumulation takes place within the soma and axons of motor neurons. However it is not yet clear whether this accumulation is a consequence or main cause of motor neurons dysfunction. Recent use of transgenic animals bearing mutations or alterations in genes coding for neurofilament sub-units or their associated proteins has not solved these questions. These findings, nevertheless have helped to understand the mechanism lying beneath these pathologies.