Understanding the mechanisms that regulate skeletal muscle mass has remained a focus of numerous researchers for many years. Recent investigations have begun to elucidate cellular signaling mechanisms that regulate skeletal muscle hypertrophy, with significant effort being focused on the Akt/mammalian target of rapamycin (mTOR) signaling pathway. The Akt/mTOR pathway plays a major role in regulating the initiation of protein synthesis after the onset of mechanical loading of skeletal muscle. Although a number of downstream substrates for Akt/mTOR have been elucidated, very little is known about the upstream mechanisms that mechanical load employs to activate the Akt/mTOR signaling pathway. Thus, the purpose of this review is to discuss potential mechanisms that may contribute to the activation of the Akt/mTOR signaling mechanism in mechanically loaded skeletal muscle.