MP2/6-311++G(d,p) and B3LYP/6-311++G(2df,p) methods were found to be able to predict the gas-phase acidities of various organic acids with a precision of 2.2 and 2.3 kcal/mol. A PCM cluster-continuum solvation method was developed that could predict the solvation free energies of various neutral, cationic, and anionic organic species in DMSO with a precision of about 2.0 kcal/mol. Using these carefully tested methods, we successfully predicted the pK(a)'s of 105 organic acids in DMSO with a precision of 1.7-1.8 pK(a) units. We also predicted the pK(a)'s of a variety of organosilanes in DMSO for the first time using the newly developed methods. This study was one of the first that employed first-principle methods for calculating pK(a)'s of unrelated compounds in organic solutions.