Gap junctions are arrays of cell-to-cell channels that allow diffusion of small molecules between neighboring cells. The individual channels are formed by the four-transmembrane connexin (Cx) proteins. Recently, multiple proteins have been found to interact at the cytoplasmic site with the most abundant connexin, Cx43, but physiological data about the role of these interactions is scarce. Here, molecular detail about Cx43 interactions is presented and the putative roles of Cx43-interacting proteins are discussed. Emphasis is on new insights into the interactions of c-Src and ZO-1 with Cx43, interacting proteins discovered within the last 2 years (drebrin, CIP85, CCN3), and feedback between gap junctions, adherens junctions (N-cadherin and catenins) and the cytoskeleton (microtubules and actin).