My research focuses on the underlying mechanisms in sleep disruptions induced by stress, neurological diseases (e.g., epilepsy and Parkinson’s disease) and psychiatric disorders, such as depression and anxiety. We are also interested in the effects of acupuncture and herbal medicines on the treatment of insomnia. Sleep-wake activities are recorded and analyzed by the electroencephalography (EEG), electromyography (EMG), gross movements and cortical temperature. Pharmacological methods by administration agonists and/or antagonists into lateral ventricle or directly into the specific brain targets through an implanted guide cannula are employed to elucidate the neural mechanisms. Our results demonstrated that epilepsy occurred at different zeitgeber time points may alter sleep homeostasis either by homeostatic factors or circadian rhythm, or both. Neuroendocrines, such as interleukin-1, corticotropin-releasing hormone and hypocretin, play important roles in these epilepsy-induced sleep disruptions. This result provides a new direction in developing novel drugs for epilepsy-induced sleep disruptions. One of our studies indicate that stress induces the enhanced release of hypocretin in the median raphe nucleus (MRN), activates the indirect GABAergic pathway in the MRN, and subsequently increases the power of theta oscillations, an index of anxiety levels. Management of the excitability of MRN by hypocretin antagonist or the electrical stimulation blocks theta oscillations and anxiety behavior. This observation further directs the new treatments for anxiety. Our studies in acupuncture demonstrate that electroacupuncture (EA) of Anmian acupoints enhances sleep by activation of vagus nerves and opioid receptors in the nucleus tractus solitarius (NTS). Low frequency EA-induced sleep enhancement is mediated by mu-opioid receptors, while high-frequency EA’s effect on sleep is mediated by kappa-opioid receptors. This result reveals the underlying mechanisms for acupuncture in the treatment of insomnia. However, one of our recent studies indicates that high-frequency EA of Feng-Chi acupoints exacerbates pilocarpine-induced epilepsy and sleep disturbances, suggesting that the indication described in ancient Chinese literatures needs to be re-examined by scientific methodology. Our goal is to elucidate the underlying mechanisms of sleep disturbances and to provide solutions for insomnia and sleep disturbances.