Recent data demonstrating the multifunctional role of serum amyloid A (SAA) in the pathogenesis of amyloidosis have yielded important insights into this potentially fatal consequence of chronic inflammation. SAA has been shown to participate in chemotaxis, cellular adhesion, cytokine production, and metalloproteinase secretion and is thus integrally involved in the disease process. In addition to its production by the liver as part of the acute phase response, SAA is also expressed by several pathologic tissues such atherosclerotic plaques, rheumatoid synovitis and in the brains of patients with Alzheimer disease. Its constitutive production in normal tissue suggests a role for SAA in host defense and tissue turnover. Many pathways are involved in the regulation of SAA, and as more becomes known about these, potential therapeutic targets may be identified. However, the prevention of secondary amyloidosis is best achieved by early and adequate treatment of patients with chronic inflammatory disorders. Suppression of the acute phase response and normalization of SAA levels are likely to significantly impact on the incidence of amyloidosis in inflammatory arthritis.