Studies of the retinoblastoma (RB) gene product suggest that it may work as a fundamental regulator to coordinate pathways of cellular growth and differentiation. One known function of retinoblastoma (Rb) protein is its ability to suppress tumorigenesis. In many different cultured tumor cells, replacement of a normal RB gene and expression of normal Rb protein results in suppression of neoplastic properties. Moreover, in humans or experimental mice, germ line mutation of the RB gene leads particularly to retinoblastomas or pituitary tumors, respectively, which demonstrates that the role of RB in tumor predisposition is specific to certain tissues. In addition to suppressing tumor formation, Rb apparently also has roles in normal development and cellular differentiation. Recent characterizations of Rb-associated proteins and proteins within the Rb family may provide some clues to exploring the complex networks in which Rb is involved.