Neurons are highly specialized cells whose connectivity at synapses subserves rapid information transfer in the brain. Proper information processing, learning, and memory storage in the brain requires continuous remodeling of synaptic networks. Such remodeling includes synapse formation, elimination, synaptic protein turnover, and changes in synaptic transmission. An emergent mechanism for regulating synapse function is posttranslational modification through the ubiquitin pathway at the postsynaptic membrane. Here, we discuss recent findings implicating ubiquitination and protein degradation in postsynaptic function and plasticity. We describe postsynaptic ubiquitination pathways and their role in brain development, neuronal physiology, and brain disorders.