This review compared the effectiveness of functional behavior assessment-based interventions (FBAI) versus non-functional behavior assessment-based interventions (NFBAI) through an examination of 24 single-case design (SCD) studies that directly compared the effects of these intervention approaches. This review also systematically examined the quality of these studies. All of the reviewed studies reported relative effectiveness of FBAI over NFBAI in reducing problem behaviors, showing a higher percentage of behavior reduction in FBAI than NFBAI conditions. None of the reviewed studies met all of the What Works Clearinghouse Design Standards for SCD (Kratochwill et al. in Single-case designs technical documentation, 2010). We discussed methods of comparing the effects of FBAI versus NFBAI and made methodological suggestions for future research in this area.