The precise wiring of the nervous system is a combined outcome of progressive and regressive events during development. Axon guidance and synapse formation intertwined with cell death and neurite pruning sculpt the mature circuitry. It is now well recognized that pruning of dendrites and axons as means to refine neuronal networks, is a wide spread phenomena required for the normal development of vertebrate and invertebrate nervous systems. Here we will review the arising principles of cellular and molecular mechanisms of neurite pruning. We will discuss these principles in light of studies in multiple neuronal systems, and speculate on potential explanations for the emergence of neurite pruning as a mechanism to sculpt the nervous system.