Gap junctions are tightly packed intercellular channels that serve a common purpose of allowing the intercellular exchange of small metabolites, second messengers and electrical signals. Connexins (Cxs) are gap junction proteins. Currently, 20 and 21 members of Cxs have been characterized in mice and humans, respectively. Connexin 43 (Cx43) is the most ubiquitously expressed type of Cx in the skin. It is produced by various different types of skin cell, such as keratinocytes, fibroblasts, endothelial and basal cells, melanocytes and dermal papilla cells. At present, more evidence indicates that Cx43 has an important role in skin repair and skin tumor development, as well as in skin cell invasion and metastasis. In this review, current knowledge regarding the regulation and function of Cx43 is summarized and the therapeutic potential of regulating Cx43 activity is discussed.