Connexins comprise gap junction channels, which create a direct conduit between the cytoplasms of adjacent cells and provide for intercellular communication. Therefore, the level of total cellular connexin protein can have a direct influence on the level of intercellular communication. Control of connexin protein levels can occur through different mechanisms during the connexin life cycle, such as by regulation of connexin gene expression and turnover of existing protein. The degradation of connexins has been extensively studied, revealing proteasomal, endolysosomal and more recently autophagosomal degradation mechanisms that modulate connexin turnover and, subsequently, affect intercellular communication. Here, we review the current knowledge of connexin degradation pathways.