Rheumatoid arthritis is chronic systemic inflammatory disease that is characterized by joint swelling and leukocyte recruitment into synovial tissue. Within the peripheral blood and synovial fluid of patients with rheumatoid arthritis there are many soluble mediators that function together to create an inflammatory environment ultimately responsible for the synovial pannus formation and subsequent joint destruction. One such group of soluble mediators present in the peripheral blood and synovial fluid of rheumatoid arthritic patients are soluble adhesion molecules. Soluble adhesion molecules are commonly formed as the result of cell surface adhesion molecule shedding due to cell stimulation, but may also be the result of de novo synthesis of truncated soluble forms of adhesion molecules. There has been debate over the function of soluble adhesion molecules in the inflammatory process. Soluble adhesion molecules have been shown to both enhance and inhibit different aspects of the inflammatory process. However, the preponderance of research studying rheumatoid arthritis has shown soluble adhesion molecules to be important regulators of leukocyte recruitment into the synovial tissue. This review will focus on the soluble adhesion molecules that have been studied in peripheral blood and synovial fluids of patients with rheumatoid arthritis. The role of different soluble adhesion molecules in the pathogenesis of rheumatoid arthritis will be discussed, as will the effects of common disease modifying anti-rheumatic therapies on their production.