β 2-Adrenoceptor agonists are the gold standard for the symptomatic treatment of asthma, resulting in quick and effective bronchodilator relief, although they are not completely free from side-effects. A range of different pharmacological approaches is being actively pursued in order to achieve relaxation of airway smooth muscle comparable to that seen with β 2-adrenoceptor agonists and by mechanisms distinct from activation of theβ-adrenoceptor without attendant side-effects. These various approaches include signalling via vasoactive intestinal polypeptide (VIP) receptors, activation of soluble and particulate guanylyl cyclase, inhibition of phosphodiesterase (PDE)3 and opening of potassium channels. The pharmacology, clinical experience and merit of each of these novel approaches are discussed.