Prescription drugs play an essential and growing role in Canada's healthcare system and the health of Canadians. But some drugs are not used correctly (misuse), used too frequently (overuse) or not used nearly enough (underuse), resulting in missed health benefits, harm to individual Canadians and unnecessary costs. In this article, we highlight lessons learned from the Health Council of Canada's synthesis of evidence and a recent symposium regarding what works to improve the appropriateness of prescribing.