Vibrational spectroscopy is a powerful technique for interrogating the structure and dynamics of liquids due to its exquisite time and spatial resolution. This dissertation exploits the vibrational technique to examine the structure and dynamics of various liquids: water, dilute mixtures of water and alcohol, neat alcohol, IL mixtures, and water surrounding DNA. Specifically, by monitoring the vibrational frequency of a reporter group as the surrounding environment changes, process called spectral diffusion, important dynamical information can be extracted. The vibrational probe of interest in this research is the OD stretch, which has been used extensively in experiments and theory. Experimental studies examining the structure and dynamics of deuterated alcohols isolated in ionic liquids (ILs) have revealed that spectral diffusion of the OD stretch of the alcohol slows slightly as the length of the alkyl chain increases. Orientational relation, however, shows a more dramatic effect as it slows with increasing alkyl chain length. Molecular dynamics (MD) simulations of isolated water, methanol, and ethanol in the 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, [emim][NTf2], IL were performed to shed insight into the nature of coupled solute-ion dynamics. Also, MD simulations of the alcohols at dilute concentration in aqueous solution were carried out to provide a comparison. The theoretical calculations of the spectral diffusion dynamics and orientational relaxation of the OD stretch of the isolated vibrational reporters in [emim][NTf2] agree well with experiment. The size of the alcohol does not affect the spectral diffusion timescales very much, while there are distinct differences between the reorientational relaxation timescales.The sensitivity of the phosphate asymmetric stretch vibrational frequency to DNA hydration was investigated with MD simulations and a spectroscopic map relating the vibrational frequency to the electrostatics of its environment. 95\% of the phosphate vibrational frequency shift in fully hydrated DNA was due to water within two hydration layers. The phosphate vibration was relatively insensitive to water in the major and minor grooves and the sodium counterions but was enormously sensitive to water interacting with the DNA backbone. Comparisons to experimental measurements on DNA as a function of relative humidity suggest that one water molecule per phosphate group likely persists at the lowest values of the relative humidity. Finally, the calculated spectral diffusion dynamics show that water in the vicinity of the DNA backbone is slowed by a factor of five, in agreement with NMR and solvation dynamics experiments, as well as previous MD simulations.