This chapter discusses the need for robust studies to validate the various aspects of telemedicine, including patient health outcomes, provider adoptions, and healthcare system economic outcomes, and highlights the importance of addressing the “digital divide” that the technologies of telemedicine create and the need for investigations to promote trust and ease of adoption of information and communication technology. We will provide a framework for primary care to develop investigational research and further validation of telemedicine adoption within clinical practice to address population health needs and randomized clinical trials for digital tools within primary care. We will outline areas of research for telemedicine, virtual and augmented reality, 5G and beyond connectivity, data privacy and security, wearable and IoT devices, user experience and accessibility, health equity and policy, and clinical outcomes and cost-effectiveness. The chapter concludes by exploring the specific use case of hypertension as an example of understanding some of the investigation needs for the telemedicine and remote consult realms.