The capacity to appropriately respond to physiological challenges or perturbations in homeostasis is a requisite for survival. It is becoming increasingly clear that long-lasting alterations in synaptic efficacy are a fundamental mechanism for modifying neuroendocrine and autonomic output. We review recent advances in our understanding of plasticity at glutamate synapses onto magnocellular neurones (MNCs) in the paraventricular and supraoptic nuclei of the hypothalamus, with a focus on the contributions of metabotropic glutamate receptors (mGluRs) to long-lasting modifications in synaptic efficacy. Special attention is paid to the role of presynaptic mGluRs as gatekeepers for metaplasticity and regulation of body fluid homeostasis. The work highlighted here provides insight into the synaptic mechanisms that couple MNC activity to physiological states.