Autoimmune diseases result from an interplay between susceptibility genes and environmental factors. These interacting etiopathogenetic components converge in a critical step preceding disease, the loss of tolerance to self. In this review, we examine the evidences linking tobacco smoking with the initiation and perpetuation of inflammation affecting both the synovial membrane and the endothelial lining in patients with rheumatoid arthritis. This disease is a compelling argument for the decisive role of environment in the triggering of a human autoimmune disease in genetically prone individuals. © 2010 Springer-Verlag.