Over the past decade, RTI International has pursued the goal of quality, inclusive, differentiated early grade literacy instruction in nearly 30 early grade reading or early grade literacy programs in low- and middle-income (LMI) countries. Across our diverse portfolio, we have supported Ministries of Education (Ministries) in diverse contexts in their development and implementation of research-based early grade literacy programs and have learned important lessons based on our experience working with Ministries to design, develop, and implement early grade literacy programs. This paper describes the core elements that we have found to improve early grade literacy instruction and learner outcomes: the approach to teaching (Teach), the availability of quality, relevant learner materials (Text), the effective use of instructional time (Time), the use of formative assessment to guide instruction (Test), and provision of instruction in the most effective language (Tongue). This paper focuses on the acquisition of literacy in alphabetic and alphasyllabic languages in the early primary years (most typically, academic levels 1 through 3) and the kinds of exposures, instruction, and support learners need to become fully literate. These are the elements of a literacy program that can be taught, that should be present in teaching and learning materials and in teacher trainings, and that relate specifically to what happens in a classroom. Many more factors contribute to literacy acquisition. However, we focus on the core elements in this paper to delve deeper and facilitate a richer discussion about these components. No one-size-fits-all approach to the development and implementation of literacy programs exists; the local context and constraints of any implementation can require adaptation and adjustments. In many cases, the fully diversified approach to early grade literacy instruction described in the classroom scenario has not yet been achieved. However, we hope that this compilation of lessons learned and best practices achieved through our experiences will help to further the efforts of all to provide high-quality, effective literacy instruction to all learners, particularly those in LMI countries.