Developmental dyslexia is a neurodevelopmental disorder characterized by an unexpected impairment in literacy acquisition leading to specific poor academic achievement and possible secondary symptoms. The multi-level framework of developmental dyslexia considers five levels of a causal pathway on which a given genotype is expressed and hierarchically transmitted from one level to the next under the increasing influence of individual learning-relevant traits and environmental factors moderated by cultural conditions. These levels are the neurobiological, the information processing and the skill level (prerequisites and acquisition of literacy skills), the academic achievement level and the level of secondary effects. Various risk factors are present at each level within the assumed causal pathway and can increase the likelihood of exhibiting developmental dyslexia. Transition from one level to the next is neither unidirectional nor inevitable. This fact has direct implications for prevention and intervention which can mitigate transitions from one level to the next. In this paper, various evidence-based theories and findings regarding deficits at different levels are placed in the proposed framework. In addition, the moderating effect of cultural impact at and between information processing and skill levels are further elaborated based on a review of findings regarding influences of different writing systems and orthographies. These differences impose culture-specific demands for literacy-specific cognitive procedures, influencing both literacy acquisition and the manifestation of developmental dyslexia.