Contractile phenotype of muscle fibres is strongly influenced by hormones, stretch and influences from the motor neurones, although cell lineage probably also plays a role. Motor neurones can affect muscle fibres by releasing neurotrophic substances and by evoking electrical activity in the muscle. For regulating contractile properties such as speed, strength and endurance it has been demonstrated that electrical activity is crucial, while the role of putative neurotrophic substances remains unclear. The signal to change is coded in the pattern of electrical activity. Thus, high amounts of activity lead to slow shortening velocity and myosin heavy chains, while low amounts of activity lead to a fast phenotype. For regulation of twitch duration frequency also plays a role, and for preventing atrophy in denervated muscles high frequency seems to be beneficial, particularly in fast muscles. Little is known about the excitation–adaptation pathway linking action potentials to expression of genes that are relevant for contractile properties. Muscle specific transcription factors of the helix–loop–helix family such as myoD and myogenin could be important for regulating genes related to metabolic profile and fibre size/strength, while their role in determining myosin heavy chain expression and classical fibre type is more uncertain.