Orton-Gillingham (OG) and Orton-Gillingham-based reading instructional programs are commonly implemented reading programs in the United States. Twelve studies that employed quasi-experimental or experimental designs are reviewed. These studies included elementary students, adolescents, and college students. Of the 12 studies, 5 reported that the OG instruction was more effective than were comparison or control interventions for all measured outcomes, 4 reported that the OG instruction was more effective for at least 1 (but not all) outcomes in comparison to other intervention(s), 2 reported that the alternate instruction was more effective than the OG instruction, and 1 reported no significant differences once covariates were included. The largest effects were reported for word attack and non-word reading outcomes, with mean effect size of .82, and comprehension outcomes, with a mean effect size of .76. Following a summary of each study, limitations of the current review and implications for future research and practice are described. Given the small number of studies, the lack of methodological rigor of the existing studies, and the inconclusive findings of the effectiveness of OG programs, additional research is needed before the scientific basis can be established.