Water is the most studied molecule in the history of scientific research, and yet much remains unknown about this structurally simple but functionally complex molecule. There is ample evidence that understanding the fundamental nature of the hydrogen bond and its response to changing chemical and thermodynamic conditions is the key to understanding water’s many properties and functions. The goal of this work was to examine the H-bond in the context of its bond angle and bond distance, and furthermore to investigate the impact that alteration of water’s bulk structure can have on biomolecules and vice versa. A two-dimensional potential energy surface was constructed for the gaseous water dimer that showed changes in the O-O distance between two H-bonded water molecules have a negligible effect on bond energy as compared to H-bond angle. This surface supports the idea that in liquid water, where O separation is known to be spatially constrained, H-bond angle plays the primary role in bond energetics. Since the decoupled OH stretching vibration is known to be a sensitive reporter of the local electronic environment of the oscillator, the OH stretch absorption of liquid water can be analyzed in terms of H-bond angles in the solution. High concentrations of the guanidinium ion were found to have a profound effect on water structure, causing a higher proportion of more linear H-bonds in solution than is found in bulk water. This finding raises the possibility that alteration of water structure may contribute to the ability of guanidinium to denature proteins in solution. Water structure under high hydrostatic pressures was also examined, and it was found that water’s ice VII form undergoes a structural rearrangement at pressures right above the ice VI to VII transition, from two H-bond populations to a single H-bond population. In addition, this work shows that hydrostatic pressures within the liquid water regime have effects on the structure of small peptides that are dependent on the identity of the side chain. This result has implications for determining the conditions under which amino acid based life can form the macromolecules and perform the chemistry necessary to remain viable.