Acute blood flow restriction (BFR) by itself or in combination with low-intensity aerobic and/or low-load resistance exercise has been shown to result in favourable effects on skeletal muscle, namely increases in muscle size and strength (Loenneke et al. 2012). These positive muscular adaptations have been observed across a wide range of populations (e.g. athletes, elderly, diseased). Previous research indicates that BFR resistance exercise stimulates muscle protein synthesis (MPS) (Gundermann et al. 2012); however, little is known about the exact cellular mechanisms behind that response on muscle protein synthesis or muscle hypertrophy. Previous research suggests that the muscle hypertrophic effect may, in part, be related to the concomitant decrease in the mRNA gene expression of E3-ligases such as MURF-1 (8 h post-decrease; Manini et al. 2011) and atrogin (Manini et al. 2011). Furthermore, Laurentino et al. (2012) have observed decreased mRNA gene expression of myostatin, with an increased expression of the follistatin isoforms following low-load resistance exercise with BFR. In a recent issue of The Journal of Physiology, Nielsen et al. (2012) presented research that suggests that the proliferation of myogenic stem cells may be an additional mechanism involved in the muscle hypertrophic response to high-frequency low-load resistance exercise with BFR. Briefly, participants performed four sets of knee extensor exercise to failure at 20% of their concentric one repetition maximum. The researchers found that performing 23 sessions of low-load BFR exercise within 19 days resulted in marked increases in muscular strength and muscle fibre cross-sectional area when measured greater than 3 days post-training. It should be mentioned that there were transient increases in muscle fibre cross-sectional area after 5 days of the intervention in both groups; however, this was thought to be due to exercise-induced cell swelling and not a reflection of true muscle hypertrophy. This is supported by the post-training data which indicated increases in muscle size and strength only in the BFR group, while the work-matched control groups’ fibre cross-sectional area was equivalent to baseline levels. These positive muscular adaptations in the BFR group were accompanied by a substantial upregulation in myogenic stem cells, resulting in nuclear additions to the exercised muscle fibre. The data reported in the Nielsen et al. (2012) investigation provides valuable insight into the acute and chronic effects of high-frequency low-load resistance training with BFR. The increased proliferation of myogenic stem cells with BFR resistance training is significant as it is thought that the myonuclear donation is required in order to have substantial increases in human muscle fibre cross-sectional area. Further support of this notion comes from their data which show positive correlations between the change in myonuclei number per fibre and muscle fibre area as well as between the relative change in myogenic stem cells per fibre and muscle fibre area. The exact reason behind the large increase in myogenic stem cell proliferation is not known, but the authors speculated that the activation and proliferation of myogenic stem cells may be acutely stimulated by BFR-induced stretch-, hypoxia-, and/or contraction-induced nitric oxide secretion. In addition, they noted that it was unlikely that the increased proliferation was due to muscle cell membrane damage because the authors did not find any visible signs of damage to the basal lamina from their laminin stainings. This finding is consistent with previous BFR studies, which indicate minimal to no muscle damage with this type of exercise. It would be interesting if future research could expand on these findings and investigate whether or not there is proliferation of myogenic stem cells and a subsequent myonuclear addition in response to low-intensity aerobic exercise in combination with BFR. This type of study would be useful as low-intensity aerobic exercise with BFR has been observed to elicit significant increases in muscle size and strength (Loenneke et al. 2012). Currently it is unknown if the mechanisms behind that effect are different to that observed with low-load resistance training. Additionally, BFR in the absence of exercise has been shown to attenuate atrophy; however, it is unclear as to the exact mechanism involved with BFR in the absence of muscle contraction. Whether or not there is a relationship between the application of BFR in the absence of muscle contraction and myogenic stem cells is unknown but might be an interesting avenue of research to explore in the future.