The phenomenon of active trans-membrane water cycling (AWC) has emerged in little over a decade. Here, we consider transport across cell membranes from the origins of its study. Historically, trans-membrane water transport processes were classified into: A) compensating bidirectional fluxes ("exchange"), and B) unidirectional flux ("net flow") categories. Recent literature molecular structure determinations and molecular dynamic (MD) simulations indicate probably all the many different hydrophilic substrate membrane co-transporters have membrane-spanning hydrophilic pathways and co-transport water along with their substrates, and that they individually catalyze category A and/or B water flux processes, although usually not simultaneously. The AWC name signifies that, integrated over the all the cell's co-transporters, the rate of homeostatic, bidirectional trans-cytolemmal water exchange (category A) is synchronized with the metabolic rate of the crucial ,-ATPase (NKA) enzyme. A literature survey indicates the stoichiometric (category B) water/substrate ratios of individual co-transporters are often very large. The MD simulations also suggest how different co-transporter reactions can be kinetically coupled molecularly. Is this (,-ATPase rate-synchronized) cycling futile, or is it consequential? Conservatively representative literature metabolomic and proteinomic results enable comprehensive free energy analyses of the many transport reactions with known water stoichiometries. Free energy calculations, using literature intracellular pressure values reveals there is an outward trans-membrane barochemical gradient of magnitude comparable to that of the well-known inward electrochemical gradient. For most co-influxers, these gradients are finely balanced to maintain intracellular metabolite concentration values near their consuming enzyme Michaelis constants. The thermodynamic analyses include glucose, , gamma-aminobutyric acid (GABA), and transporters. 2%-4% alterations can lead to disastrous concentration levels. For the neurotransmitters and GABA, very small astrocytic changes can allow/disallow synaptic transmission. Unlike the and electrochemical steady-states, the barochemical steady-state is in (or near) chemical equilibrium. The analyses show why the presence of aquaporins (AQPs) does not dissipate the trans-membrane pressure gradient. A feedback loop inherent in the opposing electrochemical and barochemical gradients regulates AQP-catalyzed water flux as an integral AWC aspect. These results also require a re-consideration of the underlying nature of . Active trans-membrane water cycling is not futile, but is inherent to the cell's "NKA system" - a new, fundamental aspect of biology.