Science educators and theorists have long argued that more specific concepts and skills of scientific domains should not be divorced from the process of scientific inquiry (Barrow 2006). As elaborated in the other chapters in this volume, proponents of inquiry-oriented instruction argue that students should engage in the same “authentic” thinking processes as practicing scientists, and that they should discover scientific knowledge through scientific investigation. For many, the debate is not whether science should be taught via inquiry, but rather how to do so. For example, some argue that inquiry learning should be organised around social problems that emerge from modern society (e.g. Sadler 2004) rather than laboratory contexts. Within particular inquiry contexts, some argue for more open-ended student-directed activities (e.g. Tamir 1983), while others have emphasised the need for guided inquiry that leads to currently accepted scientific laws and principles (Magnusson and Palinscar 1995). These debates in turn lead to more specific issues such as teacher question-answering practices (e.g. Furtak 2006) and the appropriate roles for technology (e.g. Edelson, Gordon and Pea 1999; Linn, Clark and Slotta 2003). Nonetheless, science instruction has continued to focus on relatively direct exposition of scientific facts, skills, and concepts (Olson and Loucks-Horsley 2000). This chapter briefly considers some of the challenges facing inquiryoriented instruction. It then illustrates how newer theories of cognition can be used to transform two key challenges – classroom assessment and external testing – in order to directly support the design of and participation in inquiry-oriented instruction. This illustration takes the form of assessment design principles that emerged over four annual cycles of design-based refinements of an inquiry-oriented science curriculum in one immersive educational videogaming platform.