Major developments concerning imidazoline receptor (IR) molecular biology, cell signaling, and purification of endogenous ligands have greatly expanded our understanding of the molecular nature of these proteins and of agmatine-metabolizing enzymes. The diversity of IR subtypes and the possible relationship of these receptors to the function of various organs and potential therapeutic targets in psychiatry and diabetes present new areas for discussion. The diversity of IR subtypes as well as a wide tissue distribution of imidazoline-selective binding sites has led to an appreciation that other organ systems besides the brain are also probably influenced by IR. Furthermore, the discovery and characterization of two endogenous IR ligands (agmatine and harmane) have pointed to the potential therapeutic value of these agents in unexpected areas like brain trauma and psychiatry. Agmatine acts as a neuroprotective agent in brain trauma as well as an agent capable of alleviating chronic pain, drug withdrawal syndromes, and inflammatory responses. This volume serves as a guidepost to these agents' usefulness in other unexpected areas, including diabetes and related metabolic syndromes, drug addiction, and neuropathic pain.