The combined results of ab initio electronic-structure calculations and spectroscopic investigations of jet-cooled molecules and clusters provide strong evidence of a surprisingly simple and general mechanistic picture of the nonradiative decay of biomolecules such as nucleic bases and aromatic amino acids. The key role in this picture is played by excited singlet states of πσ* character, which have repulsive potential-energy functions with respect to the stretching of OH or NH bonds. The 1πσ* potential-energy functions intersect not only the bound potential-energy functions of the 1ππ* excited states, but also that of the electronic ground state. Via predissociation of the 1ππ* states and a conical intersection with the ground state, the 1πσ* states trigger an ultrafast internal-conversion process, which is essential for the photostability of biomolecules. In protic solvents, the 1πσ* states promote a hydrogen-transfer process from the chromophore to the solvent. Calculations for chromophore–water clusters have shown that a spontaneous charge-separation process takes place in the solvent shell, yielding a microsolvated hydronium cation and a microsolvated electron. These results suggest that the basic mechanisms of the complex photochemistry of biomolecules in liquid water can be revealed by experimental and theoretical investigations of relatively small chromophore–water clusters.