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Strength and endurance training produce widely diversified adaptations, with little overlap between them. Strength training typically results in increases in muscle mass and muscle strength. In contrast, endurance training induces increases in maximal oxygen uptake and metabolic adaptations that lead to an increased exercise capacity. In many sports, a combination of strength and endurance training is required to improve performance, but in some situations when strength and endurance training are performed simultaneously, a potential interference in strength development takes place, making such a combination seemingly incompatible. The phenomenon of concurrent training, or simultaneously training for strength and endurance, was first described in the scientific literature in 1980 by Robert C. Hickson, and although work that followed provided evidence for and against it, the interference effect seems to hold true in specific situations. At the molecular level, there seems to be an explanation for the interference of strength development during concurrent training; it is now clear that different forms of exercise induce antagonistic intracellular signaling mechanisms that, in turn, could have a negative impact on the muscle's adaptive response to this particular form of training. That is, activation of AMPK by endurance exercise may inhibit signaling to the protein-synthesis machinery by inhibiting the activity of mTOR and its downstream targets. The purpose of this review is to briefly describe the problem of concurrent strength and endurance training and to examine new data highlighting potential molecular mechanisms that may help explain the inhibition of strength development when strength and endurance training are performed simultaneously.