The biochemistry of amyloidosis as it relates to clinical medicine and experimental pathology is presented. Amyloidoses are complex disorders in which normally soluble precursors undergo pathological conformational changes and polymerize as insoluble fibrils with the beta-pleated sheet conformation. Over the past 20 years, 16 biochemically diverse proteins have been identified as fibrillar constituents of amyloid deposits; in all cases the protein-protein interactions that result in amyloid fibril formation appear to be stabilized both by the structure and the microenvironment of the precursor protein. Either genetic predisposition or dysfunctions of the immune system favor amyloid fibril formation. In particular, macrophage function is a factor in the pathogenesis of many of the amyloidoses. The diagnosis of amyloidosis involves acquisition of a tissue biopsy, staining of the specimen with Congo red, and observation of classic green birefringence on polarization microscopy. The subdiagnosis of the systemic amyloidoses involves characterization of variant or monoclonal plasma amyloid precursor proteins in the context of clinical symptoms. Treatment is generally supportive, with the use of antiinflammatory therapy, dialysis, or transplantation and genetic counseling where indicated.