This systematic review gives an overview of the effects of differentiation practices on language and math performance in primary education, synthesizing the results of empirical studies (n = 21) on this topic since 1995. We extracted 78 effect sizes from the included studies. We found that using computerized systems as a differentiation tool and using differentiation as part of a broader program or reform had small to moderate positive effects on students’ performance. Between- or within-class homogeneous ability grouping had a small negative effect on low-ability students, but no effect on others. The finding that computer technology can be a useful tool to facilitate differentiated instruction is not covered in earlier reviews. Moreover, our findings emphasize that homogeneous ability grouping alone is not enough to guarantee differentiated instruction. This stresses the importance of embedding differentiation practices in a broader educational context.