Knowledge activation and knowledge building are essential for reading comprehension. Yet, how can teachers support students in accessing and applying their existing knowledge and experiences during reading? This article provides six evidence-based principles to consider during literacy instruction, which are drawn from a recent systematic literature review that examined prior knowledge activation instructional scaffolds. These principles are: (a) activate knowledge before, during, and after reading; (b) activate knowledge collaboratively; (c) support students in understanding connections between concepts; (d) support students in recognizing discrepancies between their knowledge and the text; (e) address misunderstandings; and (f) consider the amount of topic-specific knowledge that students have. These principles have the potential to shift how teachers think about the role of knowledge activation throughout the reading process.