Adolescents in the United States and their teachers face an enormous academic challenge with respect to reading comprehension. College and career readiness standards outlined in the Common Core (2012) place increased emphasis on preparing students to read increasingly complex text across a range of disciplinary content areas. At issue is how to develop the necessary skills and understandings to read the texts required of college and literacy-demanding occupations when fewer than 35% of students in secondary grades read proficiently (U.S. Department of Education, 2012, NCES 2012-457). The increased demands to read and learn from complex text and the reading proficiency levels of today's adolescents bring into sharp relief the academic chasm that exists in secondary classes (Eason, Goldbert, Young, Geist, & Cutting, 2012) and the need to engage content-area teachers in the solution. Design experiments were conducted to examine the potential and feasibility of two interventions to improve student content knowledge and reading comprehension: Team-based Learning in social studies and Critical Reading Practices (teacher-directed and student-regulated comprehension practices) in English language arts. Both studies examined common research questions including (a) the potential and feasibility of two interventions, (b) intervention refinements, and (c) receptivity and perceptions of users. This paper reports lessons learned and how design experiments shaped instructional procedures and practices. English language arts and social studies design experiments were both conducted in classrooms in three school districts in two states, representing rural, suburban, and small urban areas. Twelve social studies and seven English language arts teachers participated in the design studies. Teachers were nominated by their principal as expert teachers in their field. In order to be nominated, teachers were required to have at least three years of teaching experience, high ranking on evaluations, deep knowledge of content, and a willingness to commit to the study. A design experiment methodology was used to define and refine interventions through multiple iterations. Findings from the design experiments in English Language Arts provided extensive information regarding intervention prototype refinements. Several important recommendations emerged regarding changes to prototype interventions including (a) routines that transfer to novels and informational text, (b) increased focus on comprehension fix-up strategies, (c) lessons that explicitly teach inference-making, (d) several options for vocabulary instruction, (e) lessen emphasis on classwide discussion and increase mini-discussions during reading, (f) incorporate more extensive writing assignments, (g) increase emphasis on documenting and using textual evidence. Social Studies Findings from the design experiments and observations of typical practice identified key areas for intervention refinement in the social studies classes including, (a) expansion of vocabulary instruction in the intervention to go beyond simple definitions which were the typical practice for teachers in 51% of the observations, (b) increased supported text reading and strategies for learning content from text (text was used in typical practice only 10% of observed time), (c) expanding text comprehension instruction beyond oral questioning (used 76% of the time in typical practice), (d) increasing active student engagement in using text, discussion and problem solving about content, and identifying text evidence to support arguments, answers, and opinions, (e) providing several high quality, complex text options for instruction, (f) identifying multiple examples of broad, essential content related questions to elicit quality student discussion and deep processing of content and readings, (g) structured student discussion that includes student recording of key points and evidence. The authors' observations led them to believe that more work was needed to structure successful peer-mediated activities and discussions. They learned that developing an intervention that maps onto existing curriculum requires navigating and orchestrating may factors including differences by grades, heterogeneity in classrooms, and teacher preferences. A figure is appended.