Intercellular junctions represent the key contact points and sites of communication between neighboring cells. Assembly of these junctions is absolutely essential for the structural integrity of cell monolayers, tissues and organs. Disruption of junctions can have severe consequences such as diarrhea, edema and sepsis, and contribute to the development of chronic inflammatory diseases. Cell junctions are not static structures, but rather they represent highly dynamic micro-domains that respond to signals from the intracellular and extracellular environments to modify their composition and function. This review article will focus on the regulation of tight junctions and adherens junctions by phosphatase enzymes that play an essential role in preserving and modulating the properties of intercellular junction proteins.