Citrus aurantium (bitter orange) extract and its principal protoalkaloidal constituent p-synephrine are widely used in weight loss and weight management as well as in sports performance products. However, questions are raised frequently regarding the safety of these ingredients. The potential inherent dangers associated with the use of products containing C. aurantium extract are frequently touted, while conversely, millions of doses of dietary supplements have been consumed by possibly millions of individuals in recent years. Furthermore, millions of people consume on a daily basis various juices and food products from Citrus species that contain p-synephrine. This review summarizes current information regarding the safety of C. aurantium (bitter orange) extract and p-synephrine based on human, animal and in vitro assessments as well as receptor binding and mechanistic studies. The data indicate that based on current knowledge, the use of bitter orange extract and p-synephrine appears to be exceedingly safe with no serious adverse effects being directly attributable to these ingredients. Copyright © 2011 John Wiley & Sons, Ltd.