Clinical reasoning is a critical core competency in medical education. Strategies to support the development of clinical reasoning skills have focused on methodologies used in traditional settings, including lectures, small groups, activities within Simulation Centers and the clinical arena. However, the evolving role and growing utilization of virtual patients (VPs) in undergraduate medical education; as well as an increased emphasis on blended learning, multi-modal models that include VPs in core curricula; suggest a growing requirement for strategies or guidelines that directly focus on VPs. The authors have developed 12 practical tips that can be used in VP cases to support the development of clinical reasoning. These are based on teaching strategies and principles of instructional design and pedagogy, already used to teach and assess clinical reasoning in other settings. Their application within VPs will support educators who author or use VP cases that promote the development of clinical reasoning.