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Improvements in teachers’ pedagogical content knowledge are critical in improving science education but may be insufficient to support and sustain instructional changes. This chapter describes how contextual factors influenced teachers’ use of research-based instructional strategies learned in professional development. The research draws on survey, observational, and interview data collected from 135 teachers who participated in four different intensive professional development programs that were situated in small, rural school districts with high-need student populations and that extended over 3 years. Each program had a slightly different STEM focus, but all four programs aimed to improve teachers’ pedagogical content knowledge in science and to foster their use of research-based instructional strategies in science. Across programs, teachers’ science content knowledge, pedagogical content knowledge, and self-efficacy increased over the course of the professional development. Overall, teachers more frequently used research-based practices for teaching science. But contextual factors varied substantially across schools and districts and both fostered and hindered teachers’ science instruction. The most influential contextual factors included time for planning and collaboration, time for science instruction, administrator support, access to resources, and regional constraints. Identifying the contextual factors that influence teachers’ use of pedagogical content knowledge gained through professional development is the first step for formulating strategies for supporting and sustaining teacher change.