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E-learning is becoming a necessary skill, calling for familiarity with learning management systems. This chapter describes the construction process of the Chemistry Online Blended Learning Environment (COBLE) – a 3-year chemistry course for high-school students. The research that accompanied the COBLE was a detailed 3-year longitudinal study aimed at 23 grade 10–12 students who wished to study chemistry but could not do so in their schools. Since the founding of COBLE, four cohorts have already finished successfully, while students are enrolling for the 7th year. This chapter addresses the dynamic environment’s design and redevelopment, which succeeded to cope with rapid growth in student numbers and massive curriculum changes due to a national reform, bearing in mind that the aim was to improve self-regulated learning (SRL) of chemistry. Findings show that the design affected students’ level of SRL and constituted a major factor in their achievements and overall success. The novelty of this study is primarily related to the extent to which the environmental design influenced the students over the 3-year course, and in particular, their SRL improvement over time.