Chronic conditions are the most important cause of morbidity, mortality and health expense in the USA. Comparative effectiveness research (CER) seeks to provide evidence supporting the relative value of alternative courses of action. This research often concludes with estimates of the likelihood of desirable and undesirable outcomes associated with each option. Patients with chronic conditions should engage with their clinicians in deciding which of these options best fits their goals and context. In practicing shared decision-making (SDM), clinicians and patients should make use of CER to inform their deliberations. In these ways, SDM and CER are interrelated. SDM translates CER into patient-centered practice, while CER provides the backbone evidence about options and outcomes in SDM interventions. In this review, we explore the potential for a SDM-CER synergy in improving healthcare for patients with chronic conditions. © 2013 Future Medicine Ltd.