Purpose: In this article, we respond to Catts and Kamhi's (2017) argument that reading comprehension is not a single ability. Method: We provide a brief review of the impact of strategy instruction, the importance of knowledge in reading comprehension, and possible avenues for future research and practice. Results: We agree with Catts and Kamhi's argument that reading comprehension is a complex endeavor and that current recommended practices do not reflect the complexity of the construct. Knowledge building, despite its important role in comprehension, has been relegated to a back seat in reading comprehension instruction. In the final section of the article, we outline possible avenues for research and practice (e.g., generative language instruction, dialogic approaches to knowledge building, analogical reasoning and disciplinary literacy, the use of graphics and media, inference instruction) for improving reading-comprehension outcomes. Conclusions: Reading comprehension is a complex ability, and comprehension instruction should reflect this complexity. If we want to have an impact on long-term growth in reading comprehension, we will need to expand our current repertoire of instructional methods to include approaches that support the acquisition and integration of knowledge across a variety of texts and topics.