Dialysis-related amyloidosis (DRA) is a clinical syndrome of pain, loss of function and other symptoms due to the deposition of amyloid consisting of β(2)-microglobulin (β(2)m) in the musculoskeletal system. The condition is seen in patients who suffer from chronic kidney disease and are treated with hemodialysis for a long time. Even though β(2)m easily can be manipulated to form amyloid in laboratory experiments under non-physiological conditions the precise mechanisms involved in the formation of β(2)m-amyloid in patients with DRA have been difficult to unravel. The current knowledge which is reviewed here indicates that conformational fluctuations centered around the D-strand, the DE-loop, and around the cis-configured Pro32 peptide bond are involved in β(2)m amyloidosis. Also required are highly increased concentrations of circulating β(2)m and possibly various post-translational modifications mediated by the pro-inflammatory environment in uremic blood, together with the influence of divalent metal ions (specifically Cu(2 +)), uremic toxins, and dialysis-enhanced redox-processes. It seems plausible that domain-swapped β(2)m dimers act as building blocks of β-spine cross-β -sheet fibrils consisting of otherwise globular, roughly natively folded protein. An activated complement system and cellular activation perpetuate these reactions which due to the affinity of β(2)m-amyloid for the collagen of synovial surfaces result in the DRA syndrome.