A historical review and current clinical findings relating a new type of amyloid material to long term hemodialysis are presented, followed by a review of the biochemistry, metabolism and involvement of beta 2-M and theories for the pathogenesis of HRA. The syndromes develop several years after replacement of renal function by dialysis, and seem to be progressive over time. Preliminary clinical studies utilizing more permeable artificial kidney membranes suggest their potential usefulness in the prevention of HRA syndromes, specifically those attributable to persistent elevation of serum beta 2-M; however, caution in their employment is advised. The development of effective treatment for long-term hemodialysis patients afflicted with CTS, arthritic symptoms and skeletal manifestations of HRA is unfortunately constrained by deficiencies in our knowledge. Renal transplantation has been demonstrated to reduce the elevated serum beta 2-M levels in hemodialysis patients to normal; however, the effectiveness of this modality to treat clinical manifestations of HRA has not been reported. Thus, efficacious treatment strategies have lagged considerable behind diagnostic techniques. Intensive research is needed as the story of this new form of renal osteodystrophy unfolds.