Three imidazoline receptor subtypes (I₁, I₂, and I₃) have been proposed and the understanding of each has seen differing progress over the decades. I₁ receptors partially mediate the central hypotensive effects of clonidine-like drugs. I₂ receptors associate with several distinct proteins, but the identities of these proteins remain elusive. The understanding of I₃ receptors is relatively limited. Existing data suggest that I₃ receptors may represent a binding site at the Kir6.2-subtype ATP-sensitive potassium channels in pancreatic β-cells and may be involved in insulin secretion. Despite the elusive nature of their molecular identities, recent progress on drug discovery targeting imidazoline receptors (I₁ and I₂) demonstrates the exciting potential of these compounds to elicit neuroprotection and to treat various disorders such as hypertension, metabolic syndrome, and chronic pain.[1]