Response to intervention (RTI) must be combined with comprehensive cognitive assessment to identify children with learning disabilities. This article presents the Cognitive Hypothesis Testing (CHT) model for integrating RTI and comprehensive evaluation practices in the identification of children with reading disabilities. The CHT model utilizes a scientific method approach for interpreting cognitive and neuropsychological processes together with evaluation of ecological and treatment validity data to develop targeted interventions for students who do not respond to standard academic interventions. A case study highlights how CHT practices can lead to effective interventions for a child who did not respond to a phonologically based reading intervention. In addition, discriminant analyses of 128 children with reading disabilities revealed the presence of Global, Phonemic, Fluency-Comprehension, and Orthographic subtypes. Results suggest subtypes show disparate cognitive profiles that differentially impact their reading achievement, supporting our contention that individual assessment of cognitive processing strengths and weaknesses is not only necessary for identifying children with reading disabilities but also can lead to individualized interventions designed to meet their unique learning needs. (Contains 1 figure and 4 tables.)