The brain is considered a major site for microRNA (miRNA) expression; as evidenced by several studies reporting microarray data of different brain substructures. The hypothalamus is among the brain regions that plays a crucial role in integrating signals from other brain nuclei as well as environmental, hormonal, metabolic and neuronal signals from the periphery in order to deliver an adequate response. The hypothalamus controls vital functions such as reproduction, energy homeostasis, water balance, circadian rhythm and stress. These functions need a high neuronal plasticity to adequately respond to physiological, environmental and psychological stimuli that could be limited to a specific temporal period during life or are cyclic events. In this context, miRNAs constitute major regulators and coordinators of gene expression. Indeed, in response to specific stimuli, changes in miRNA expression profiles finely tune specific mRNA targets to adequately fit to the immediate needs through mainly the modulation of neuronal plasticity.