Relationship between biological responses and binding affinities at I(1)/I(2)/I(3) imidazoline receptors of compounds with imidazoline, pyrroline or oxazoline moieties was studied by 2D-QSAR, 3D-QSAR and quantitative pharmacophore development approaches. Since the I(1) imidazoline receptor is involved in central inhibition of sympathicus that produce hypotensive effect, the I(2) receptor is allosteric modulator of monoamine oxidase B (MAO-B) and the I(3) receptor regulates insulin secretion from pancreatic β-cells, design and synthesis of selective I(1)/I(2)/I(3) imidazoline ligands are very important for the development of new effective therapeutic agents. New agonists and antagonists with high selectivity for I(1)/I(2)/I(3) imidazoline receptor classes have been recently synthesized and examined. The present review will highlight the main chemical diversity and pharmacophore features of selective I(1)/I(2)/I(3) imidazoline receptor ligands.