This paper provides an overview of contemporary computational protocols toward accurate prediction of acidities in the gas and aqueous phase. The performance of various density functional theory (DFT) methods and ab initio composite procedures, such as the G3MP2(+) method, for the prediction of gas-phase acidities of a range of neutral and cationic acids is presented. Various methods for solution pKa predictions are also reviewed where the emphasis is on thermodynamic cycle-based methods that combine ab initio or experimental gas-phase energies with solvation free energies from continuum solvent models. The prediction of accurate solvation free energies, especially for ionic species, represents the bottleneck for accurate pKa prediction via the direct or absolute method. The success and limitations of alternative thermodynamic cycles are discussed and some of the difficulties and future challenges associated with the applications of these methods on more complicated molecules are also highlighted. (C) 2011 John Wiley & Sons, Ltd. WIREs Comput Mol Sci 2011 1 649-660 DOI: 10.1002/wcms.43