A study of the regioselectivity of the photochemical [2+2] cycloaddition of triplet enones with a series of ground-state electron-rich and electron-poor alkenes using density functional theory (DFT)-based reactivity descriptors is presented. Using the concepts of local softness combined with a local hard and soft acids and bases principle and a softness matching approach, the regioselectivity of this reaction can only be explained in the case of the interaction of the triplet enones with electron-rich alkenes. In the next part, the regioselectivity was assessed within the framework of conceptual spin-polarized conceptual DFT, considering response functions of the system's external potential v, number of electrons N, and spin number N-s (with N-s being the difference between the number of alpha and beta electrons in the spin-polarized system). Within this theory, the concepts of local spin philicity and donicity are introduced. Using the spin philicity concept, the regioselectivity can almost be completely interpreted as resulting from the interaction of the site on the alkene with the highest spin philicity (i.e., lowest destabilization upon increasing spin number) with the site showing the highest change of spin number on the enone expected to result in the largest stabilization of this species.