In the short time since the hypocretin/orexin peptide system was discovered,^1,2 a remarkable body of evidence has accumulated indicating this system's important role in regulating feeding, energy metabolism and arousal.^3-6 Considerable progress has also been made identifying the CNS targets and actions of the two hypocretin/orexin peptides (Hcrt/Orx-A and -B) [cf 7]. We have been interested in understanding the actions of Hcrt/Orx on brainstem cholinergic and monoaminergic systems since these systems are involved with controlling arousal and sleep. Considering the extensive innervation by Hcrt/Orx afferents⁸ and the robust expression of orexin receptor message in these structures,⁹ it is likely that important components of the wake-promoting and REM suppressing abilities of Hcrt/Orx^10,11 are mediated through actions on these systems.^12-14 Here we discuss some of our recent findings concerning Hcrt/Orx actions on both the cholinergic and non-cholinergic neurons of the laterodorsal tegmental (LDT) nucleus which form part of the ascending cholinergic reticular system.^15,16.