The work in this dissertation focuses on the computational analysis of the thermodynamics of anions in the gas phase and in aqueous solution to provide unique insights into the chemistry of a range of biologically and geochemically relevant chemical species. This often involves calculating properties for these species such as electron affinities and hydration free energies of the anions, which can be difficult or impossible to obtain experimentally. Systems of interest in this work include small peptides, enzyme-catalyzed biological reactions, and the gas phase and solvation energetics of a variety of anionic species including CO2-, H-, X- (halides), OX- (hypohalites), and YH- (chalcogen hydrides). The peptide work, performed largely with the composite correlated molecular orbital theory G3(MP2) method, is compared directly to experiments conducted with low-energy collision-induced dissociation negative ion mode mass spectrometry. Isotope fractionation studies, of significant use in many geochemical applications, are conducted on the overall reaction by the alanine transaminase enzyme (+H3NCH(CH3)COO? + ?OOCCH2CH2C(O)COO? ? CH3C(O)COO? + +H3NCH(CH2CH2COO?)COO?) in order to predict that 13C preferentially collects in the C2 site of pyruvate over alanine by 9‰ at equilibrium. This prediction, calculated from gas phase- and aqueous-optimized clusters with explicit H2O molecules at the MP2/aug-cc-pVDZ with and without the COSMO self-consistent reaction field for implicit solvation, is reflected in simpler models: without explicit solvation, with simpler analogues formaldehyde and methylamine, and from canonical functional group frequencies and reduced masses for R2C=O and R2CH-NH2. Solvation studies of the CO2-, H-, X-, OX-, and YH- anions and corresponding neutrals gave adiabatic electron affinities, reduction potentials, and gas phase and aqueous acidities that are generally in excellent agreement with experiment. These studies used a variety of computational methods, including heavy application of coupled cluster calculations with the Feller-Peterson-Dixon method to obtain high accuracy thermodynamic values. Absolute hydration free energies are determined for neutral and anionic species clustered with 4 to 8 explicit H2O molecules using a supermolecule-continuum approach.