The concept of precision medicine involves tailoring medical interventions to each patient’s specific needs, considering factors such as their genetic makeup, lifestyle, environment and response to therapies. The emergence of digital twin (DT) technology is anticipated to enable such customization. The healthcare field is, thus, increasingly exploring the use of digital twins (DTs), benefiting from successful proof of concept demonstrated in various industries. If their full potential is realized, DTs have the capability to revolutionize connected care and reshape the management of lifestyle, health, wellness and chronic diseases in the future. However, the realization of DTs’ full potential in healthcare is currently impeded by technical, regulatory and ethical challenges. In this chapter, we map the current applications of DTs in healthcare, with a primary focus on precision medicine. We also explore their potential applications in clinical trial design and hospital operations. We identify the key enablers of DTs in healthcare and discuss the opportunities and barriers that foster or hinder their larger and faster diffusion. By providing a comprehensive view of the current landscape, opportunities and challenges, we aim to contribute to DTs’ ongoing development and help policymakers facilitate the growth of DTs’ application in healthcare.