Most tobacco-focused clinical trials are based on locally-conducted studies that face significant challenges to implementation and successful execution. These challenges include the need for large, diverse, yet still representative study samples. This often means a protracted, costly, and inefficient recruitment process. Multi-site clinical trials can overcome some of these hurdles but incur their own unique challenges. With recent advances in mobile health (mHealth) and digital technologies, there is now a promising alternative: Remote Trials. These trials are led and coordinated by a local investigative team, but are based remotely, within a given community, state, or even nation. The remote approach affords many of the benefits of multi-site trials (more efficient recruitment of larger study samples) without the same barriers (cost, multi-site management, regulatory hurdles). The Coronavirus Disease 2019 (COVID-19) global health pandemic has resulted in rapid requirements to shift ongoing clinical trials to remote delivery and assessment platforms, making methods for the conduct of remote trials even more timely. The purpose of the present manuscript it to provide an overview of available methods for the conduct of remote tobacco-focused clinical trials as well as illustrative examples of how these methods have been implemented across recently completed and ongoing tobacco studies. We focus on key aspects of the clinical trial pipeline including remote: 1) study recruitment and screening, 2) informed consent, 3) assessment, 4) biomarker collection, and 5) medication adherence monitoring.