The electronic health record (EHR) is an omnipresent aspect of healthcare in the United States. Compared with paper-based clinical records, the ability to easily share and record clinical data has significantly increased efficacy within the healthcare system. Despite increased efficacy, the EHR has “a large number of challenges that arguably limit the optimal use.” To address these challenges, a group of 24 Penn Medicine affiliated researchers compiled a series of 20 short essays describing use of the EHR. The study was led by PISC Senior Scholar John H. Holmes, PhD, FACE, FACMI, and features Senior Scholars Mary Regina Boland, MA, MPhil, PhD, and George Demiris, PhD, FACMI. Each essay addresses specific aspects of EHR use such as usability and usefulness, data quality, and clinical research, with a goal to “provide an exhaustive reference for those who use the EHR in clinical and research contexts.” In addition to serving as a valuable resource, these essays have the potential to drive the design and implementation of new EHR systems.