This article quantitatively summarizes experimental and quasi-experimental studies on teaching students with mathematics difficulties (MD) published between 2000 and 2014, research that was available following earlier syntheses. It reports the analysis of effect sizes of 25 intervention studies on participant characteristics, intervention parameters, domains of mathematics interventions, and instructional approaches and components. Results indicate that several participant characteristics (e.g., grade level and level of mathematics difficulties) and intervention parameters (e.g., methodological soundness, intervention agent, and grouping) mediated the treatment effects. In addition, different types of instructional approaches and several instructional components contributed to the improvements in mathematics performance in students with MD.