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Literacy is a gateway to education, and yet universal literacy remains an aspiration rather than a reality. The science of reading has, however, made significant progress in understanding the key factors that impact development. Five relevant factors can be identified. The first factor is the developmental focus of models. Here the richness and dynamic nature of development is central. Models must clearly explain change and phenomena such as bi- and multilingualism. A second factor concerns bioecological influences on development. Stronger models include understandings of the complexity of gene–environment interactions in development. A third pertinent factor concerns the precise nature of the learning task facing the beginner reader, and in particular the influence of distinct orthographies. A fourth factor concerns the coherent exposition of the cognitive processes involved in “word-level” and “text-level” reading processes. Finally, contextual effects on literacy are profound. Historical and politicoeconomic forces are often linked to wide country- and region-based differences in literacy. A detailed treatment of what is known about effective interventions for struggling readers can be built on the basis of this theorizing. Here, evidence from meta-analysis suggests that both the word-level decoding and text-level comprehension aspects of reading development can be measurably improved through evidence-based interventions. For word-level interventions studies focusing on phonics currently furnish the most secure evidence of impact. For text-level comprehension, interventions focusing on oral language development and text-based meta-cognitive strategy appear the most efficacious. Measure of treatment effects for such interventions show modest but reliable impacts on development and form the basis of ongoing efforts to optimize interventions.