Water is the lubricant of life. Despite the fact that all life takes place in water, the treatment of water at the molecular level was not thought to be essential. Biology textbooks show proteins in front of a black background (“biology in vacuo”). However, water is not just a passive spectator solvent in biological processes, but has a vital function in most biomolecular and cellular processes. Water’s flexible network enables it to adapt its structure and dynamics. Hydration water makes significant contributions to the structure and energy of proteins and provides a responsive surrounding which allows for conformational changes. In particular, water may hold the key to the way proteins interact, fold (and misfold in ‘amyloidic’ diseases such as Parkinson’s and Alzheimer’s), bind substrates, and aggregate. Self-assembly of proteins is controlled by a delicate interplay between hydrophobic and hydrophilic interactions. Water at protein interfaces (hydration water or interfacial water) has been shown to thermodynamically stabilize the native structure of bio-macromolecules, to affect protein flexibility, and to contribute to molecular recognition in enzyme catalysis. Protein-water interactions are now known to shape the “free energy folding funnel” that drives protein folding. Connecting solvation dynamics with biomolecular function within RESOLV will open the way to achieving breakthroughs from understanding protein misfolding and formation of amyloid fibrils to rational drug design and de novo enzyme synthesis.