Strained-layer heterojunctions and superlattices have recently shown tremendous potential for device applications because of their flexibility for tailoring the electronic band structure. We present a theoretical model to predict the band offsets at both lattice-matched and pseudomorphic strained-layer interfaces. The theory is based on the local-density- functional pseudopotential formalism, and the “model solid approach” of Van de Walle and Martin. The results can be most simply expressed in terms of an “absolute” energy level for each semiconductor, and deformation potentials that describe the effects of strain on the electronic bands. The model predicts reliable values for the experimentally observed lineups in Si/Ge, GaAs/InAs, and ZnSe/ZnS systems, and can be used to ex-plore which combinations of materials and configurations of the strains will lead to the desired electronic properties.