Among the soluble factors that regulate skeletal muscle function, Transforming Growth Factor type Beta 1 (TGF-beta 1) is one of the most studied. This factor inhibits myogenesis and regeneration by regulating the activity and function of satellite cells (SCs). Indeed, TGF-beta has a central role in muscle pathologies in which there is development of fibrosis and/or atrophy of skeletal muscle. Thus, in this review we present the critical and recent antecedents regarding the mechanisms and cellular targets involved in the effects of TGF-beta 1 in the muscle, in pathological processes such as the inhibition of regeneration, fibrosis and atrophy. In addition, an update on the development of new strategies with therapeutic potential to inhibit the deleterious actions of TGF-beta in skeletal muscle is discussed.