Patterned neuronal activity in early postnatal life can regulate the acquisition of the mature morphological and electrophysiological properties of neurons. Many properties of motor neurons are developmentally regulated and may be influenced by epigenetic factors. The pattern of activation of motor neurons can regulate axon terminal morphology and synaptic efficacy at the neuromuscular junction. Motor neuron morphology and synaptic connections can also be modified by exposure to specific hormones in the early postnatal period. The acquisition of mature physiological and anatomical properties is paralleled by the acquisition of specific molecular properties. Recent experiments using molecular markers for motor neuron differentiation indicate that motor neurons undergo activity-dependent development during a circumscribed period in early postnatal life. Normal motor neuron differentiation requires a normal pattern of neuronal activity in early postnatal life. Differentiation also requires activation of the NMDA receptor over the same time period. The activity-dependent development of morphological, electrophysiological and molecular properties of motor neurons is similar to activity-dependent development in the vertebrate visual system. The neuromuscular system may provide an accessible system for characterizing the molecules subserving the translation of patterned neuronal activity into mature neuronal phenotype.