Clinical decision support (CDS) in electronic prescribing (eRx) systems can improve the safety, quality, efficiency, and cost-effectiveness of care. However, at present, these potential benefits have not been fully realized. In this consensus white paper, we set forth recommendations and action plans in three critical domains: (1) advances in system capabilities, including basic and advanced sets of CDS interventions and knowledge, supporting database elements, operational features to improve usability and measure performance, and management and governance structures; (2) uniform standards, vocabularies, and centralized knowledge structures and services that could reduce rework by vendors and care providers, improve dissemination of well-constructed CDS interventions, promote generally applicable research in CDS methods, and accelerate the movement of new medical knowledge from research to practice; and (3) appropriate financial and legal incentives to promote adoption.