Interruptions pose a significant safety hazard for health care providers performing complex tasks, such as signout or medication administration. However, as prior research has pointed out, many interruptions are necessary for clinical care, making it difficult for safety professionals to develop approaches to limiting the harmful effects of interruptions. Reviewing the literature on interruptions from the psychology and informatics fields, this study identifies several key variables that influence the relationship between interruption of a task and patient harm. The authors provide several recommendations, based on human factors engineering principles, to mitigate the effect of interruptions on patient care. A case of an interruption leading to a medication error is discussed in this AHRQ WebM&M commentary.