Multi-tiered frameworks have been implemented in schools nationwide for over 20 years. The goal of a multi-tiered system of supports (MTSS) is to prevent the further development of academic, behavioral, or social–emotional difficulties by providing students with support in response to their needs. MTSS includes universal screening and progress monitoring, multilevels of academic or behavioral interventions, data-based decision-making, and school-wide implementation. Although generally effective, there is less research that examines culturally and linguistically relevant practices in the interventions and assessment systems used. This chapter will describe how the MTSS framework can be effectively combined with culturally relevant education (CRE) to create a culturally and linguistically responsive MTSS framework (CL-MTSS) with emergent bilingual (EB) students. It provides practical recommendations for educators seeking to implement a CL-MTSS framework, including the challenges that may arise.