Whether for the generation or application of evidence to guide healthcare decisions, the success of evidence-based medicine is grounded in principles common to engineering. In the Learning Healthcare System envisioned by the Institute of Medicine's (IOM) Roundtable on Evidence-Based Medicine, evidence emerges as a natural by-product of care delivery, which is thoroughly documented, pooled for continuous monitoring and analysis, integrated with insights from related studies, and fed back seamlessly to improve the consistency and appropriateness of care decisions by clinicians and their patients. Drawing from lessons shared at the IOM/NAE symposium, Engineering a Learning Healthcare System, this paper provides an overview of the state-of-play in health care today, some of its key challenges, the vision and features of a learning healthcare system, applicable commonalties and principles from engineering, and potential collaborative opportunities moving forward to the benefit of both fields.