Over the last several years the involvement of the innate immune system in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE) has become well established. As systemic sclerosis (SSc; scleroderma) shares clinical features and autoantibodies with SLE, investigation has recently focused on the role of innate immunity in SSc. This has been supported by recent genetic studies. However, unlike SLE and other related autoimmune diseases, SSc patients suffer from pathologic fibrosis of skin and internal organs. The fibrotic component of SSc shares several features with syndromes following environmental exposures to agents such as organic solvents, silica dust and bleomycin. Recent work in SSc and these related fibrotic diseases have identified several areas in which innate immunity can stimulate inflammation as well as fibrosis. This article will focus on the recent discoveries identifying a prominent role of cells of the innate immune system, pattern recognition receptors, and activation of dendritic cells in the pathogenesis of SSc.