To optimize its function, skeletal muscle exhibits exceptional plasticity and possesses the fundamental capacity to adapt its metabolic and contractile properties in response to various external stimuli (e.g., external loading, nutrient availability, and humoral factors). The adaptability of skeletal muscle, along with its relatively large mass and high metabolic rate, makes this tissue an important contributor to whole body health and mobility. This adaptational process includes changes in the number, size, and structural/functional properties of the myofibers. The adaptations of skeletal muscle to exercise are highly interrelated with dietary intake, particularly dietary protein, which has been shown to further potentiate exercise training-induced adaptations. Understanding the molecular adaptation of skeletal muscle to exercise and protein consumption is vital to elicit maximum benefit from exercise training to improve human performance and health. In this review, we will provide an overview of the molecular pathways regulating skeletal muscle adaptation to exercise and protein, and discuss the role of subsequent timing of nutrient intake following exercise.