The maturation of striated muscle in primary cultures closely parallels the formation of striated muscle in vivo. Primary cultures thus serve as model systems for the study and manipulation of various aspects of muscle development including the regulation of gene expression, myofibril assembly, myocyte fusion, and myotube contraction. The following protocols provide instructions for the preparation of skeletal muscle cultures from either day 10 embryonic pectoralis muscle or day 2 somites and segmental plate mesoderm. Both methods will yield well-striated, multinucleated, contracting myotubes (Fig. 1) (1–4). Also included is a protocol for the preparation of cardiac cultures from day 7 embryonic heart. This method will yield well-striated, contracting cardiomyocytes (Fig. 1) (5,6).