In 1937, the Spanish neuroscientist and artist Ramón y Cajal commented on an apparent trial and error period of chaotic dendritic and axonic growth, with most of the resulting connections destined to disappear. But over subsequent decades the prevailing concept among neurobiologists and behavioral biologists was that synaptic connections increase with learning. Peter then rigorously showed in 1979 that after birth and an initial burst of growth in synapse numbers in human infants, there is a regression. He and his collaborators went on to show that these connections disappear at different times, with different kinetics, in distinct regions of the brain. The physical housekeeping task of this process is not small – selecting and eliminating billions of inactive synapses in the developing brain. In some regions of the brain, such as the visual system, the clearance mechanism seems to be relatively rapid over weeks or months. In other regions of the brain, for example in areas of higher cognitive function like the frontal cortex, this process of elimination is apparently more prolonged. What process or system has the intrinsic ability to identify and clear unused synapses? What has the ability to do this in a refined way, by targeting the correct contact sites, and without leaving dead cells and debris behind?