As water is one of the most abundant chemical compounds in biological systems, a detailed description of energetic and structural aspects involving the interaction of biomolecules with water is essential for understanding them. Here, we review work-primarily done in our laboratories-focusing on the interaction of individual water molecules with a range of model biomolecules, including peptides and nucleotides. We evaluate water binding energies, water binding sites, the effect of water on biomolecule structure, and we discuss where this research is heading. (C) 2009 Elsevier B.V. All rights reserved.