We have carried out a DFT computational investigation of the catalytic mechanism of caspases, using a model system obtained from the crystallographic structure of caspase-7. In particular, we have considered the activation of the catalytic dyad (His-144 and Cys-186) and the breaking of the substrate peptide bond. We have suggested a novel mechanism for the catalytic activation, which is rather different from that usually proposed for other cysteine proteases. Following our hypothesis the activation mechanism consists of three distinct kinetic steps leading to the protonation of the catalytic His-144 and the deprotonation of Cys-186, which is activated as a nucleophile. This mechanism corresponds to a rather complex multiple proton transfer where the substrate aspartate and one water molecule act as proton shuttles. The role played by the aspartate group explains the high specificity of caspases toward substrates containing the aspartate residue that behaves as a cofactor. Apart from acting as proton shuttles and "assisting" almost all proton transfers, the two water molecules included in our model form a complex network of hydrogen bonds that involve enzyme and substrate and stabilize the charges developing on the substrate during of the reaction. We have demonstrated the existence of an alternative reaction channel leading directly from the initial complex to the peptide bond cleavage in a single kinetic step. However, this reaction pathway can be considered very unlikely since it is characterized by a high energy barrier.