Generating explanations for oneself in an attempt to make sense of new information (i.e., self-explanation) is often a powerful learning technique. Despite its general effectiveness, in a growing number of studies, prompting for selfexplanation improved some aspects of learning, but reduced learning of other aspects. Drawing on this recent research, as well as on research comparing self-explanation under different conditions, we propose four constraints on the effectiveness of self-explanation. First, self-explanation promotes attention to particular types of information, so it is better suited to promote particular learning outcomes in particular types of domains, such as transfer in domains guided by general principles or heuristics. Second, self-explaining a variety of types of information can improve learning, but explaining one's own solution methods or choices may reduce learning under certain conditions. Third, explanation prompts focus effort on particular aspects of the to-be-learned material, potentially drawing effort away from other important information. Explanation prompts must be carefully designed to align with target learning outcomes. Fourth, prompted self-explanation often promotes learning better than unguided studying, but alternative instructional techniques may be more effective under some conditions. Attention to these constraints should optimize the effectiveness of self-explanation as an instructional technique in future research and practice.