Cell volume is determined genetically for each cell lineage, but it is not a static feature of the cell. Intracellular volume is continuously challenged by metabolic reactions, uptake of nutrients, intracellular displacement of molecules and organelles and generation of ionic gradients. Moreover, recent evidence raises the intriguing possibility that changes in cell volume act as signals for basic cell functions such as proliferation, migration, secretion and apoptosis. Cells adapt to volume increase by a complex, dynamic process resulting from the concerted action of volume sensing mechanisms and intricate signaling chains, directed to initiate the multiple adaptations demanded by a change in cell volume, among others adhesion reactions, membrane and cytoskeleton remodeling, and activation of the osmolyte pathways leading to reestablish the water balance between extracellular/intracellular or intracellular/intracellular compartments. In multicellular organisms, a continuous interaction with the external milieu is fundamental for the dynamics of the cell. It is in this sense that the recent surge of interest about the influence on cell volume control by the most extended family of signaling elements, the G proteins, acquires particular importance. As here reviewed, a large variety of G-protein coupled receptors (GPCRs) are involved in this interplay with cell volume regulatory mechanisms, which amplifies and diversifies the volume-elicited signaling chains, providing a variety of routes towards the multiple effectors related to cell volume changes.