The COVID-19 pandemic has been a catalyst for the implementation of decentralized clinical trials (DCTs) enabled by digital health technologies (DHTs) in the field while curtailing in-person interactions and putting significant demands on health care resources. DHTs offer improvements in real-time data acquisition remotely while maintaining privacy and security. Here, we describe the implications of technologies, including edge computing, zero-trust environments, and federated computing in DCTs enabled by DHTs. Taken together, these technologies-in the setting of policy and regulation that enable their use while protecting the users -extend the scope and accelerate the pace of clinical research.