Tiered instructional supports are on a steep growth trajectory in the US and getting underway internationally as a means to providing equitable education to all student groups. In the US, the Department of Education funded the expansion of multi-tiered system of support (MTSS) through school and personnel improvement grants to states. This retrospective article examines the history of MTSS and California’s significant investment to scale up the practice statewide, with an eye to identifying key issues that are likely to surface in other such ambitious state efforts. We examine the infrastructure support methodology to develop local capacity to support school-level implementation with measured fidelity. We present some preliminary results from a small sample comparison study that demonstrate students’ academic achievement increased when the California MTSS efforts resulted in implementation with adequate fidelity. These findings suggest long-term replication of this initiative will mirror other student-level impact studies showing positive gains on measures of academic progress, in this case, English Language Arts and Math.