For decades, investigators have conducted innovative research on shared decision-making (SDM), helping patients and clinicians to discuss health decisions and balance evidence with patients' preferences for possible outcomes of options. In addition, investigators have developed and used rigorous methods for conducting comparative effectiveness research (CER), comparing the benefits and risks of different interventions in real-world settings with outcomes that matter to patients and other stakeholders. However, incorporating CER findings into clinical practice presents numerous challenges. In March 2012, we organized a conference at Washington University in St Louis (MO, USA) aimed at developing a network of researchers to collaborate in developing, conducting and disseminating research about the implementation of CER through SDM. Meeting attendees discussed conceptual similarities and differences between CER and SDM, challenges in implementing CER and SDM in practice, specific challenges when engaging SDM with unique populations and examples of ways to overcome these challenges. CER and SDM are related processes that emphasize examining the best clinical evidence and how it applies to real patients in real practice settings. SDM can provide one opportunity for clinicians to discuss CER findings with patients and engage in a dialog about how to manage uncertainty about evidence in order to make decisions on an individual patient level. This meeting highlighted key challenges and suggested avenues to pursue such that CER and SDM can be implemented into routine clinical practice. © 2013 MC Politi, ML Clayman, A Fagerlin, JL Studts & V Montori.