Systematic reviews and meta-analyses of randomized controlled studies conclude that virtual patient simulations are consistently associated with higher learning outcomes compared to other educational methods. However, we cannot assume that students will learn from simply exposing students to the simulations. The instructional features that are integrated before, during and after the simulations may affect learning and performance as much as or more than the simulation and how those features are used. Here, we examine the design and development of "NERVE": A virtual patient simulation created to give medical students standardized experiences in interviewing, examining, and diagnosing virtual patients with cranial nerve disorders. We depict key design features of the simulation and discuss how two sets of design research studies were completed to improve the total learning experience, including the virtual patient simulations and the instructional features incorporated with the simulations.