Conformational disease represents an intriguing but devastating class of neurodegenerative disorders that includes prion disease, Alzheimers disease, Parkinsons disease and Huntingtons disease. Although symptoms, on-set times and prognosis among the diseases can vary markedly, the deposition of neurotoxic protein aggregates is a significant commonality, and as such is an attractive therapeutic target. Understanding the mechanisms of protein misfolding and deposition in these conditions is critical to developing effective diagnostic and therapeutic agents. This review serves as an update for the sister publication “Protein Conformational Misfolding and Amyloid Formation: Characteristics of a New Class of Disorders that Include Alzheimers and Prion Diseases” in Curr. Med. Chem. 2002, 9, 1751-62, and focuses primarily on recent developments in understanding prion disease and Alzheimers disease in context with other conformational disease. New research in amyloid-related therapeutic strategies is also discussed.