How to draw the boundaries of disease is both a theoretical and a practical problem. Many theoretical accounts of disease hold that for disease to be present there must be biological dysfunction. Biological functioning might be low, high, or anything in between. In order to distinguish disease from health, there needs to be a way to establish, at least roughly, where the line between function and dysfunction lies. Furthermore, in order to satisfy such theoretical accounts of disease, this must be done in an objective and value-free way. The line-drawing problem is a challenging theoretical problem. It is also a serious practical problem. Many today are worried that the lowering of thresholds to diagnose and treat disease has led to overdiagnosis, overtreatment, and patient harm. Others are concerned that the failure to distinguish diseases properly from risk-based conditions that have no dysfunction has also led to overdiagnosis. This chapter considers how to distinguish disease from health, function from dysfunction, and disease from risk-based conditions, for theoretical and practical purposes. It considers the role that the risk of negative consequences and symptoms might play in drawing these lines. It explores the recent trend to look at how physicians draw these lines in medical practice. It also considers whether lines in medical practice should be drawn on a continuum of biological functioning, or on different axes altogether.