Evaluating the impact of instructional innovations and coordinating instruction, assessment, and testing present complex tensions. Many evaluation and coordination efforts aim to address these tensions by using the coherence provided by modern cognitive science perspectives on domain-specific learning. This paper introduces an alternative framework that uses emerging situative assessment perspectives to align learning across increasingly formal levels of educational practice. This framework emerged from 2 design studies of a 20-hr high school genetics curriculum that used the GenScope computer-based modeling software. The 1st study aligned learning across (a) the contextualized enactment of inquiry-oriented activities in GenScope, (b) “feedback conversations” around informal embedded assessments, and (c) a formal performance assessment; the 2nd study extended this alignment to a conventional achievement test. Design-based refinements ultimately delivered gains of nearly 2 SD on the performance assessment and more than 1 SD in achievement. These compared to gains of 0.25 and 0.50 SD, respectively, in well-matched comparison classrooms. General and specific assessment design principles for aligning instruction, assessment, and testing and for evaluating instructional innovations are presented.