CCN proteins are small secreted cysteine-rich proteins containing up to four individual structural modules including an insulin-like growth factor binding domain, a von Willebrand Factor type C motif, a thrombospondin type I module and a carboxyl-terminal cystine knot. Actually, there is a large body of evidence suggesting that members of the CCN protein family encompass an expansive repertoire of functions in crucial areas including control of development, cell fate, angiogenesis, tumorigenesis, osteogenesis, cell adhesion, mitogenesis, migration, chemotaxis, and cell survival. Moreover, this family is supposed to modulate signalling of integrins, transforming growth factor-betas, bone morphogenetic proteins, vascular endothelial growth factor, Notch and factors that mediate signals via the canonical Wingless-type MMTV integration site family. However, several of these properties are not substantiated by experimental data but were deduced from proteins sharing one or more of the structural modules with these proteins. In this review, the actual knowledge of biological activities and molecular involvement of CCN proteins in maintenance of liver health and in initiation and progression of hepatic diseases is summarized and discussed.