Within the Response-to-Intervention framework, students who fail to profit from high-quality general education instruction, accommodations, and supplemental instruction progress to a more intensive intervention program, sometimes referred to as "Tier III." This article describes a problem-solving approach to designing such intensive, data-based, and scientifically supported interventions for students with pervasive reading problems who have failed to respond to less rigorous services. The application of well-established (i.e., progress monitoring) and emerging methods (i.e., brief experimental analysis) for optimizing interventions are described. Two case studies are provided to illustrate how these techniques may be combined to implement Tier III interventions. (Contains 2 figures, 2 footnotes and 2 tables.)