Although difficult to quantify, there is known widespread variation in the way that best available evidence is applied in clinical practice. The reasons for gaps between evidence and practice are complex, and efforts to improve uptake are unlikely to be successful if they are one-dimensional or focus on individual health professionals. This article provides contextual reference for articles in this Supplement in addressing how and why clinical variation exists, the importance of reducing it and strategies to drive a more streamlined approach to evidence-based care in Australian health care systems.