Orexin/hypocretin neurones in the posterior hypothalamus are mutually connected with noradrenergic, serotonergic, dopaminergic, histaminergic, and cholinergic neurone systems. They activate these targets by direct post-synaptic and indirect pre-synaptic mechanisms and in turn receive inhibitory feedback and excitatory feed forward control. With respect to behavioural state control, orexin/hypocretin neurones are conducting the orchestra of biogenic amines. This review highlights the role of these players in the control of energy administration, sleep-wake architecture, cortical activation, plasticity, and memory functions in health and disease.