Fibrosis is an important health problem, and its pathogenetic principles are still largely unknown. It can develop either spontaneously, or, more frequently, as a consequence of various underlying diseases. Irrespective of the primary cause, however, fibrotic tissue is always infiltrated by mononuclear immune cells. In most instances the reason for the attraction of these cells to fibrotic tissue and their proliferation remains to be determined; however their cytokine profile shows clear-cut proinflammatory and profibrotic characteristics. In this review, we discuss the innate and adaptive immune reactions associated with the development of fibrosis and the molecular basis of the profibrotic mechanisms taking place in systemic sclerosis (scleroderma), arteriosclerosis and peri-silicone mammary implant fibrosis.