Neurodegenerative diseases are characterized by a relentlessly progressive loss of the functional and structural integrity of the central nervous system. In many cases, these diseases arise sporadically and the causes are unknown. The abnormal aggregation of protein within the cytoplasm or the nucleus of brain cells represents a unifying pathological feature of these diseases. There is increasing evidence for nuclear dysfunction in neurodegenerative diseases. How this relates to protein aggregation in the context of "cause and effect" remains to be determined in most cases. Co-ordinated nuclear function is predicated on the activity of distinct nuclear subdomains, or nuclear bodies, each responsible for a specific function. If nuclear dysfunction represents an important etiopathological feature in neurodegenerative disease, then this should be reflected by functional and/or morphological alterations in this nuclear compartmentalization. For most neurodegenerative diseases, evidence for nuclear dysfunction, with attendant consequences for nuclear architecture, is only beginning to emerge. In this review, I will discuss neurodegenerative diseases in the context of nuclear dysfunction and, more specifically, alterations in nuclear bodies. Although research in this field is in its infancy, identifying alterations in the nucleus in neurodegenerative disease has potentially profound implications for elucidating the pathogenesis of these disorders.