High-intensity interval training (HIT) induces numerous physiological adaptations that resemble traditional endurance training despite a low total exercise volume (2). As little as six sessions of HIT over two weeks, totaling ∼15 min of “all out” cycle exercise (∼600 kJ total work), increases the maximal activity of mitochondrial enzymes and improves performance during tasks that rely heavily on aerobic energy provision (3). Low-volume HIT also promotes improvements in markers of metabolic control during matched-work exercise that are comparable to endurance training despite marked differences in total exercise volume and training time commitment (1). These data suggest that HIT may be a potent and time-efficient strategy to induce skeletal muscle metabolic adaptations and improve functional exercise capacity. Little is known regarding the molecular processes that regulate mitochondrial biogenesis in response to HIT but evidence is accumulating to suggest that peroxisome proliferator-activated receptor γ coactivator (PGC)-1α is involved. An acute bout of HIT (4 x 30 sec “all out” cycling interspersed with 4 min of recovery) increased the activation of 5’AMP-activated protein kinase and p38 mitogen-activated protein kinase, two kinases which can directly activate PGC-1α, and led to a robust increase in PGC-1α mRNA measured 3 hours into recovery (4). The majority of PGC-1α was detected in cytosolic fractions at rest but acute HIT increased nuclear PGC-1α protein 3 h into recovery, a time point that coincided with increased mRNA expression of mitochondrial genes, and this was followed by an increased mitochondrial protein content and enzyme activity at 24 h recovery (5). Many low-volume HIT studies have employed extreme variable-load exercise interventions (e.g., repeated Wingate Tests) that may not be safe or well tolerated by certain individuals. Little et al. (6) recently showed that 2 wk of a more “practical” model of HIT (6 sessions x ~10 x 1 min repeats at ~90% maximal heart rate, separated by ~1 min of recovery) increased muscle oxidative capacity and improved endurance performance. Low-volume HIT studies in persons who might be at risk for cardiometabolic disorders or patients with chronic disease are very limited. However, a recent study showed that six sessions of the practical HIT model over 2 wk improved estimated insulin sensitivity in previously sedentary, overweight individuals (7). Insulin sensitivity was calculated based on single fasting glucose and insulin measurements and therefore primarily reflects hepatic as opposed to peripheral insulin sensitivity. It was also recently shown that low-volume HIT was effective and well tolerated in people with type 2 diabetes (8). Two weeks of HIT reduced average 24-h blood glucose concentration and postprandial glucose excursions, measured via continuous glucose monitoring under standardized diet but otherwise free-living conditions. Given that “lack of time” is the most commonly cited barrier to regular exercise participation, it is tempting to speculate that low-volume HIT may represent a time-efficient alternative to traditional endurance training. While the preliminary evidence from small, short-term studies are intriguing, large-scale studies are clearly needed to resolve whether low-volume HIT is a realistic, time-efficient exercise alternative to improve health and reduce the risk of cardiometabolic disease.