The number of sets in a resistance training program remains a major point of discussion and controversy. Studies prior to 1998 demonstrated inconsistent findings between single-set and multiple-set programs; however, recent evidence suggests that multiple sets promote additional benefits following short- and long-term training. The rationale supporting multiple sets is that the number of sets is part of the exercise volume equation, and the volume of exercise is crucial in producing the stimulus necessary to elicit specific physiological adaptations. The purpose of this paper is to present an overview of recent resistance training studies comparing single and multiple sets. However, it should be noted that studies to date have been conducted in young and middle-aged adults, and it remains to be determined if the additional benefits accrued with multiple-set training also occurs for older adults, especially the frail elderly.