CCN2, formerly known as connective tissue growth factor, was discovered in 1991. Soon after its discovery, CCN2 was shown to be upregulated in response to the profibrotic cytokine transforming growth factor (TGF) β and to be constitutively overexpressed in fibrotic conditions. These early observations led to the hypothesis that CCN2 was a key regulator of fibrosis. However, only recently have data been generated that directly demonstrate this hypothesis. This review summarizes these observations and suggests a mechanism of action for CCN2.