Exercise results in highly specific physiological adaptations. Resistance exercise increases muscle mass and force production, while endurance exercise increases aerobic capacity. As the physical and chemical signals underlying this specificity become better understood, scientists are beginning to identify the key molecular effectors of exercise specificity. This review focuses on how variations in load, metabolic stress, and calcium flux are transduced to increases in muscle mass and endurance capacity. Specific attention is paid to the mammalian target of rapamycin, AMP-activated protein kinase, and the calcium-calmodulin-activated protein kinases, and the way these proteins interact during concurrent training.