Most muscle tissue of the body arises from embryonic mesoderm. Paraxial mesodermal cells adjacent to the neural tube form blocks of cells called somites. Skeletal muscles, excluding those of the head and limbs, develop from mesodermal somites, whereas skeletal muscle in the head and limbs develop from general mesoderm. Somites give rise to myoblasts. A myoblast is a muscle-forming stem cell that migrates to different regions in the body and then fuse(s) to form a syncytium, or myotube. As a myotube is formed from many different myoblast cells, it contains many nuclei, but has a continuous cytoplasm. This is why skeletal muscle cells are multinucleate, as the nucleus of each contributing myoblast remains intact in the mature skeletal muscle cell. However, cardiac and smooth muscle cells are not multinucleate because the myoblasts that form their cells do not fuse.

Gap junctions develop in the cardiac and single-unit smooth muscle in the early stages of development. In skeletal muscles, ACh receptors are initially present along most of the surface of the myoblasts, but spinal nerve innervation causes the release of growth factors that stimulate the formation of motor end-plates and NMJs. As neurons become active, electrical signals that are sent through the muscle influence the distribution of slow and fast fibers in the muscle.

Although the number of muscle cells is set during development, satellite cells help to repair skeletal muscle cells. A satellite cell is similar to a myoblast because it is a type of stem cell; however, satellite cells are incorporated into muscle cells and facilitate the protein synthesis required for repair and growth. These cells are located outside the sarcolemma and are stimulated to grow and fuse with muscle cells by growth factors that are released by muscle fibers under certain forms of stress. Satellite cells can regenerate muscle fibers to a very limited extent, but they primarily help to repair damage in living cells. If a cell is damaged to a greater extent than can be repaired by satellite cells, the muscle fibers are replaced by scar tissue in a process called fibrosis. Because scar tissue cannot contract, muscle that has sustained significant damage loses strength and cannot produce the same amount of power or endurance as it could before being damaged.

Smooth muscle tissue can regenerate from a type of stem cell called a pericyte, which is found in some small blood vessels. Pericytes allow smooth muscle cells to regenerate and repair much more readily than skeletal and cardiac muscle tissue. Similar to skeletal muscle tissue, cardiac muscle does not regenerate to a great extent. Dead cardiac muscle tissue is replaced by scar tissue, which cannot contract. As scar tissue accumulates, the heart loses its ability to pump because of the loss of contractile power. However, some minor regeneration may occur due to stem cells found in the blood that occasionally enter cardiac tissue.