In the past decade there have been major improvements in the design, use, and effectiveness of point-of-care clinical decision support (CDS) systems to improve quality of care for patients with diabetes and related conditions. Advances in data exchange, data security, and human factors research have driven these improvements. Current diabetes CDS systems have high use rates, high clinician/user satisfaction rates, and have measurably improved glucose control, blood pressure control, and cardiovascular risk trajectories in adults with diabetes. As diabetes care increasingly relies on complex biomarker-driven risk prediction methods to optimize care goals and prioritize treatment options based on potential benefit to an individual patient, CDS systems will become indispensable tools to guide clinician and patient decision-making. In this study we describe specific challenges that must be addressed further to improve the design, implementation, and effectiveness of primary care diabetes CDS systems in coming years.