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The conference theme wisely states that “continued refinement will not be enough.” As university-based teacher educators, we could not agree more that substantive overhaul of teaching contexts should be the aim of reform, rather than superficial adjustments to traditional practice. Accordingly, we present a comparative case study conducted in the context of a three-year professional development program for 146 in-service elementary science teachers in two U.S. states based on the research question: How do teachers' epistemic orientations relate to their experiences in professional development for the construction of knowledge generation environments? Findings suggest that epistemic orientation influences what teachers choose to learn, and epistemic orientation also influences what teachers choose to enact in practice, creating iterative opportunities for reflexivity.