The purpose of this systematic literature review was to summarize single-case intervention studies involving paraprofessional-implemented systematic instruction for students with disabilities. In the 19 reviewed studies, 60 paraprofessionals received training to implement systematic instruction with most learning naturalistic language strategies, least-to-most prompting, pivotal response training, or discrete trial training. Researchers delivered paraprofessional training in a majority of cases using both didactic and experiential training methods. Paraprofessionals primarily taught students with autism spectrum disorder and focused on social/communication skills in a one-to-one instructional arrangement. The majority of studies demonstrated positive effects on paraprofessional implementation of systematic instruction and student outcomes. Implications for practice, limitations, and areas for future research are addressed.