This systematic literature review examined the research on prior knowledge and its activation to ascertain how these terms are defined, what specific techniques have been empirically investigated, and the conditions under which prior knowledge activation facilitated students’ comprehension. Fifty-four articles met the inclusion criteria and revealed that the terms prior knowledge and prior knowledge activation were often vaguely defined. Further, 30 unique techniques for activating readers’ prior knowledge representing eight different categories were identified. Those categories were open-ended prompts, procedural or strategic supports during reading, visual representations, analogical reasoning, text alteration, augmented activation, extratextual activities, and spontaneous activation. Techniques meant to facilitate knowledge activation prior to reading were most common, although the prompting of students’ existing knowledge was beneficial during and after reading as well. Variability in the effectiveness of activation techniques was related, in part, to the amount, accuracy, and specificity of students’ knowledge. Based on the key findings identified in this review, recommendations for future inquiry are forwarded, including suggested definitions of prior knowledge and prior knowledge activation.