Quantum mechanical techniques play a very important role in TiO2 photocatalysis. Recent advances in heterogeneous photocatalysis have produced a number of interesting surface phenomena, reaction products and various novel photocatalysts with improved properties than the standard TiO2 photocatalyst. Many of these phenomena have not been yet explained at the molecular level. Quantum mechanical calculations appear promising as a means of describing the mechanisms and the product distributions of the photocatalytic degradation reactions of organic pollutants in both gas and aqueous phases. Since quantum mechanical methods utilize the principles of particle physics, their use may be extended to the design of new photocatalysts. This paper presents the use of quantum mechanical techniques in TiO2 photocatalysis by using certain theoretical models. Surface active species responsible of the oxidation of organic compounds were determined to be hydroxyl radicals. The determination of the mechanisms and the product distributions of the photocatalytic degradation reactions in both gas and aqueous phases were explained by using phenols + OH reaction model. Bare and salicylic acid modified TiO2 cluster models were used to describe the design of novel photocatalysts. The relations between the degradability and molecular structure were discussed in terms of the DFT-based reactivity descriptors for monosubstituted phenol derivatives.