A multitude of factors can contribute to the occurrence of an athletic injury. In determining injury etiology, the importance of various factors may be difficult to assess, yet gaining an understanding of the manner by which they combine to produce injury advances knowledge of the injury process. Some (risk) factors may be necessarily present for injury to occur, whereas others may simple be markers of additional, unrecognized causal factors. This article outlines the concepts of interaction and confounding and describes the methods used in their assessment and control. With the emergence of multifactorial models of injury etiology, a proper assessment of interaction and confounding are important to the sport medicine researcher and practitioner seeking to assess causation.