Over the past 50 years, research on children and adults with learning disabilities has seen significant advances. Neuropsychological research historically focused on the administration of tests sensitive to brain dysfunction to identify putative neural mechanisms underlying learning disabilities that would serve as the basis for treatment. Led by research on classifying and identifying learning disabilities, four pivotal changes in research paradigms have produced a contemporary scientific, interdisciplinary, and international understanding of these disabilities. These changes are (1) the emergence of cognitive science, (2) the development of quantitative and molecular genetics, (3) the advent of noninvasive structural and functional neuroimaging, and (4) experimental trials of interventions focused on improving academic skills and addressing comorbid conditions. Implications for practice indicate a need to move neuropsychological assessment away from a primary focus on systematic, comprehensive assessment of cognitive skills toward more targeted performance-based assessments of academic achievement, comorbid conditions, and intervention response that lead directly to evidence-based treatment plans. Future research will continue to cross disciplinary boundaries to address questions regarding the interaction of neurobiological and contextual variables, the importance of individual differences in treatment response, and an expanded research base on (a) the most severe cases, (b) older people with LDs, and (c) domains of math problem solving, reading comprehension, and written expression.