Efficient cell communication is a prerequisite for the coordinated function of tissues and organs. In vertebrates, this communication is mediated by a variety of mechanisms, including the exchange of molecules between cells, and between cells and the extracellular medium, via membrane channels made of connexin and pannexin proteins. These channels are a necessary component of all human tissues. Here, we review the biological essentials of the connexin and pannexin families, and the roles of these proteins in the function of cells which are central to major human diseases. We then discuss how connexins and pannexins participate in human pathology, and the clinical perspectives that this knowledge opens.