Gap junctions and hemichannels are formed by a family of proteins called connexins. Till date up to twenty one different connexins have been characterized and their expression was observed to be spatio-temporally regulated. Gap junctions and hemichannels are involved in transfer of a variety of less than 1 kDa small molecules such as, ions, small metabolites, cAMP, ATP, IP3, prostaglandins, etc. Post-translational modifications of connexins and their interaction with other proteins are reported to be the key regulators of channel functions. Studies during the past decade or so, suggest the physiological important of connexin hemichannels mediating the communication between the cell and its environment. Molecules conveyed through the hemichannels elicit a variety of signaling pathways and influence cellular functions such as, cell cycle, tissue homeostasis, migration, mechanotransduction, oxidative stress. The purpose of the current review is to compile the reported studies so far and provide a general overview in our understanding how the molecular transfer through hemichannels regulates cellular signaling and functions.