Publisher Summary This chapter describes myofiber specification and survival. Skeletal muscle development is characterized by an orderly progression of molecular signals leading to generation of heterogeneous muscle fibers. Adult skeletal muscle retains a considerable degree of plasticity, which makes the muscle capable of adopting specific phenotypic properties in response to a wide range of factors including physical activity, injury, stimulation by motor neurons, oxygen and nutrient supply, and changes in hormone levels. Fiber type is an essential determinant of muscle function and alteration in fiber composition represents a major component in the muscle degeneration associated with muscle diseases. Adult skeletal muscle fibers are classified according to their relative velocities of contraction (Type I or II, respectively). Slow (Type I) and fast (Type II) fiber types are named according to the unique myosin heavy chain (MyHC) isoform they express. In addition to myosin heavy chain, each fiber type expresses distinct proteins comprising the contractile apparatus, calcium-sequestering components, and metabolic enzymes, so that relatively skeletal muscle-specific proteins, such as actin are expressed in all myofibers.