Design-based research methodology was used to guide a line of research to develop, implement, revise, and evaluate the ESCOLAR online science curriculum for middle school students, including general education students, English language learners (ELs) primarily of Hispanic origin, and students with high-incidence learning disabilities (LD). The iterative research approach was carried out in three stages with multiple steps per stage: (1) Stage 1, or informed exploration, identified and described the problem under investigation; (2) Stage 2, or enactment, redesigned previously developed online science units, implemented each unit in case studies, and completed a feasibility evaluation; and (3) Stage 3, or evaluation of local impact, documented the efficacy of the science curriculum with a randomized controlled trial. The present chapter focuses on the second and third stages, demonstrating the process by which the ESCOLAR curriculum was repeatedly refined with input from stakeholders, and then examined for feasibility of implementation, usefulness in helping teachers engage with students, and efficacy in deepening student science knowledge. Data were drawn from multiple sources, including teacher logs, student and teacher surveys, web analytics, student notebooks, content assessments, and focus groups. Results indicate that the ESCOLAR curriculum was feasible to implement, useful, and effective, and may now be adopted as an evidence-based intervention to enhance science learning among diverse students. The data-driven, design-based research methodology proved to be a practical framework, and underscored the critical importance of considering all stakeholders in the process of curriculum design, refinement, and evaluation. This chapter offers a model for the development of constructivist science instructional materials for ELs and students with LD using online, multimedia technology.