Beta2-microglobulin has been demonstrated to be a major constituent of amyloid fibrils in dialysis-related amyloidosis. However, the molecular pathogenesis of this complication remains unknown. Several lines of evidence suggest that P2-microglobulin is not an innocent bystander, but plays an active role in the development of dialysis-related amyloidosis. The evidence remains inconclusive, however, as to whether it is intact or modified P2-microglobulin which is amyloidogenic and contributes to bone and joint destruction. Recent biochemical and immunohistological studies have revealed a new modification of (32-microglobulin in amyloid fibrils, the advanced glycation end products formed nonenzymatically between aldoses and proteins. Further study has suggested that the interaction of advanced glycation end product-modified P2-microglobulin with monocytes/macrophages gives a plausible, albeit incomplete, explanation for the mechanism of bone and joint destruction in dialysis-related amyloidosis. This review focuses on new aspects of the pathogenesis of dialysis-related amyloidosis.