Resistance training (RT) is the main method of exercise for improving strength and skeletal muscle mass (i.e., muscle hypertrophy; ACSM, 2009). In order to promote such adaptations, high-intensity resistance training (HI-RT) with loads above 60% of one repetition maximum (1-RM) are typically recommended (ACSM, 2009). To further maximize increases in strength and muscle hypertrophy, it has been suggested repetitions to muscular failure (Jacobson, 1981; Rooney et al., 1994; Schott et al., 1995; Drinkwater et al., 2005), which can be defined as the inability to move a specific load beyond a critical joint angle (i.e., sticking point; Drinkwater et al., 2005) or as incapacity to complete a repetition in a full range of motion due to fatigue (Izquierdo et al., 2006). Some studies suggest that HI-RT to muscular failure promotes greater activation of motor units (MUs) compared to no failure HI-RT (Willardson, 2007; Akima and Saito, 2013). During a HI-RT session, MUs recruitment pattern follows the size principle, in which the low threshold MUs are recruited first, followed by high threshold MUs (Henneman, 1957). It has been speculated that even more high excitability threshold MUs, composed predominantly of type IIx muscle fibers, are recruited when repetitions are performed to failure, possibly due to fatigue in MUs (Willardson, 2007). In fact, RT to failure might promote increased electromyography (EMG) activity, which suggests increased recruitment of high threshold MUs (Akima and Saito, 2013), even when RT is performed at low intensities (Pincivero et al., 2006). In this regard, it is believed that recruiting as many MUs as possible results in maximal gains in muscle hypertrophy and strength on the target muscles (Wernbom et al., 2007). Despite a logical rationale, it is unclear if RT to failure is really necessary. Few studies directly compared RT to failure and no failure on muscle activation and strength. Results of these studies are conflicting, with some studies finding superiority for RT to failure and others showing no significant differences (Drinkwater et al., 2005; Izquierdo et al., 2006; Looney et al., 2015). Additionally, none of these studies assessed muscle hypertrophy. Based on the current literature, it is still unclear if RT to muscular failure is really necessary to maximize increases in muscle strength and hypertrophy compared to no repetition failure. Thus, the purpose of this manuscript is to discuss the effects of RT to failure on MUs recruitment and adaptive responses (i.e., increases in strength and muscle mass), providing rationale as to why RT to failure might differently affect muscle adaptations in different populations.