Water is required to hydrate molecules, but under cold conditions water freezes and under dehydrating conditions water evaporates--thus presenting a dilemma for organisms that live in extreme environments. Organisms have developed various strategies for protection against extreme temperatures and dehydration. In this review, we describe how the interaction of water and 2 natural cryoprotectants, namely glycerol and sugars, can be studied at the molecular level. Techniques using infrared spectroscopy and computation are described. In the case of glycerol, H-bonding of water to the OH groups of glycerol limits the amount of water available to form ice and prevents crystallization at low temperatures. For aldohexopyranose sugars, the different isomeric forms have different water H-bonding networks, which are consistent with isomeric-dependent activities. By studying the strategies used in nature, derivatives for use in food preservation can be more readily developed.