The authors report findings of a best-evidence synthesis of the effects of mathematics instruction on the mathematics skills of students with emotional and behavioral disorders. The goal of the synthesis was to extend previous research by (a) detailing independent variables, instructional components, and outcome measures for each study; (b) analyzing study outcomes using improvement rate difference and percentage of nonoverlapping data; and (c) summarizing literature on mathematics interventions conducted with students with emotional and behavioral disorders over four decades (from 1968 to present). Highly effective mathematics intervention studies conducted with students with emotional and behavioral disorders, limitations, and future research directions are presented and discussed.