Few studies and reports in the body of literature have directly addressed the issue of whether resistance exercise sets should be performed to failure. Research has clearly demonstrated the superiority of performing multiple sets vs. single sets for increases in maximal strength. However, there is little direct evidence to decide conclusively whether or not multiple sets should be performed to failure. Therefore, the purpose of this research note was to discuss what is currently known concerning the application of training to failure and to stimulate further research on this topic. Although not essential for increases in muscular characteristics such as strength and hypertrophy, training to failure might allow advanced lifters to break through training plateaus when incorporated periodically into short-term microcycles. Because muscular hypertrophy is a key contributor to long-term increases in maximal strength, advanced lifters should consider training to failure occasionally. The potential mechanisms by which training to failure might provide an advantage are through greater activation of motor units and secretion of growth-promoting hormones. However, training to failure is not an effective stimulus without lifting at a sufficient intensity (percentage of 1 repetition maximum). Furthermore, training to failure should not be performed repeatedly over long periods, due to the high potential for overtraining and overuse injuries. Therefore, the training status and the goals of the lifter should guide the decision-making process on this issue.