Plastic changes in synaptic transmission are thought to underlie learning and memory formation. However, changes in synaptic function are only meaningful in the context of stable baseline function. Accumulating evidence suggests that homeostatic signaling systems actively stabilize synaptic transmission in response to neural activity perturbation. Homeostatic mechanisms control both presynaptic and postsynaptic function. Here, we review recent advances in the field of presynaptic homeostatic plasticity (PHP). We discuss PHP in the context of basic mechanisms controlling neurotransmitter release, highlight emerging similarities between different synapses in different species, and summarize new insights into the molecular mechanisms underlying this evolutionary conserved form of synaptic plasticity.