Dear Editor, we appreciated reading the article by Fisher et al. (2014), entitled “The effects of pre-exhaustion, exercise order, and rest intervals in a full-body resistance training intervention”, published in the November 2014 issue of Applied Physiology, Nutrition, and Metabolism (APNM). This article determined the effects of a 12-week pre-exhaustion training intervention on muscular strength and body composition, comparing chronic adaptations between 3 groups: a pre-exhaustion group, a group performing the same exercises in the same order with moderate rest intervals between exercises, and a group performing the same exercises in a different order. The results showed no significant difference betweengroup effects for strength in chest press (1.32, 1.67, and 1.25 effect size), leg press (1.15, 1.36, and 1.89 effect size), or pull-down (1.82, 1.49, and 1.54 effect size) exercises, or for lean body mass (0.41 ± 1.08; –0.34 ± 3.37; –0.40 ± 0.60 kg) changes in pre-exhaustion group without rest interval and pre-exhaustion group with 60 s of rest interval between exercises and control group, respectively. The conflicting results regarding the hypothesis of the preexhaustion method originally proposed by Jones (1970) and the results of Fisher et al. (2014) on muscle performance and body composition changes can be, at least in part, explained by the lack of a gold-standard and/or most appropriate methods to analyze important variables regarding muscle hypertrophy and training. For example, the authors mention the recommendations of the American College of Sport Medicine (ACSM) for trained individuals, a recommendation based on the totality of the research literature. However, these authors suggest that single set resistance training leading to failure is far more time-efficient to increase muscle strength, and even acknowledge that this can be an alternative recommendation to increase muscle strength. However, for trained subjects, it is important to note that resistance training volume can increase the magnitude of muscle strength improvements (Krieger 2010). Moreover, 2 acute studies of Gentil et al. (2007) and Augustsson et al. (2003) revealed that the pre-exhaustion method does not increase muscle electromyographic activity. However, Junior et al. (2010) found that when the pre-exhaustion method was performed not to failure, the magnitude of motor units’ recruitment was higher when a single-joint exercise preceded a multijoint exercise. It has also been shown that muscle strength can increase even without a significant increase in muscle electromyographic activity (evaluated as the root mean square of the electromyography (EMG) signals) (Watanabe et al. 2014). It has been proposed that muscle hypertrophy can be achieved by the pre-exhaustion method based on the hypothesis that a target muscle can be exhausted with an isolation exercise preceding a compound exercise without rest (Schoenfeld 2013). Thus, thismethodwould increase the time under tension andmetabolic stress, a method that has been widely and empirically used by bodybuilders (Schoenfeld 2013). The metabolic stress manifested by accumulation of metabolites, such as lactate and H+ ions, and acute muscle hypoxia associated with resistance training can mediate hypertrophic adaptations, such as cellular swelling and alterations in local myokines, including interleukin-6 (Schoenfeld 2013). In this sense, considering the possible higher metabolic stress induced by the pre-exhaustion method, it is surprising that no metabolic measures or any other valuable markers of hypertrophy were obtained in the study of Fisher et al. (2014). Moreover, to draw precise conclusions regarding muscle hypertrophy, magnetic resonance and ultrasound should be used, while this was not the case. In our opinion it is premature to assume that pre-exhaustion training offers no greater benefit than a traditional resistance training approach, at least formuscle hypertrophy and for strengthwhen more sets are incorporated. Although the authors mention the lack of dietetic control, this is clearly a study limitation. Also, the lack of modifications in body composition may also be the result of a very low-volume training, considering the trained background of the studied subjects. It has been widely shown that training-induced improvements will be reduced as training progresses (Rhea 2004). The study should also provide more details regarding the training background of participants as this can result in significant variations. Additionally, there is no mention of the presence of high responders versus low responders in each group. This may also help to explain the results. For example, Garcia et al. (2014) found that the allocation of the groups resulted in bias because more high responders were unintentionally located in the multiple-sets group as compared with a group submitted to a tri-set method. This may also confound data interpretation. Thus, the identification of responders and nonresponders to resistance training may help to avoid data misinter-