An area of continuing interest in medicinal chemistry is the design, synthesis and pharmacological evaluation of ligands which bind at adrenoceptor subtypes, which include alpha 1A , alpha 1B ,alpha 1D ; alpha 2A , alpha 2B , alpha 2C beeta 1 , beeta 2 , beeta 3 and possibly beeta 4 subtypes. The selective blockade or stimulation of these receptor subtypes is of on-going pharmacological and medicinal interest. However, the design principles for ligand differentiation at these subtypes still need further development. This review focuses on alpha 1 adrenoceptors with a concentration on literature over the past five years. Structural, physiological and therapeu-tic aspects of the alpha 1A , alpha 1B and alpha 1D subtypes are discussed together with ligands binding to these receptor subtypes. Approaches to alpha 1 adrenoceptor ligand design based on known ligands and on receptor docking are evaluated. A new combined approach using pharmacophores and receptor docking affords possibilities for deeper insights into achieving small molecule binding selectivity.