The cysteinyl leukotrienes (cys-LTs), i.e. LTC(4), LTD(4) and LTE(4), trigger contractile and inflammatory processes through the specific interaction with cell surface receptors belonging to the purine receptor cluster of the rhodopsin family of the G protein-coupled receptor (GPCR) genes. Cys-LTs have a clear role in pathophysiological conditions such as asthma, allergic rhinitis and other nasal allergies, and have been implicated in a number of inflammatory conditions including cardiovascular and gastrointestinal diseases. Pharmacological studies have identified two classes of cys-LT receptors (CysLT(1) and CysLT(2)) based on their sensitivity to CysLT(1) selective antagonists, albeit there is evidence for additional subtypes. Molecular cloning of the human CysLT(1) and CysLT(2) receptors has confirmed both their structure as putative seven transmembrane domain G protein-coupled receptors and most of the previous pharmacological characterization. The rank order of potency of agonist activation for the CysLT(1) receptor is LTD4 > LTC4 > LTE4 and for the CysLT(2) receptor is LTC4 = LTD4 > LTE4. The CysLT(1) receptor is most highly expressed in spleen, peripheral blood leukocytes, interstitial lung macrophages and in airway smooth muscle. The CysLT(2) receptor is mostly expressed in heart, adrenals, placenta, spleen, peripheral blood leukocytes and less strongly in the brain. Gene cloning of CysLT(1) and CysLT(2) receptors has renewed the attention on the cys-LTs field and will, hopefully, encourage future studies on the regulation of CysLT receptors expression and the dissection of their signalling pathways. Furthermore, the peculiar pattern of expression of the two receptor subtypes will promote the discovery of new functions for cys-LTs in physiological and pathological conditions. Only CysLT(1) selective receptor antagonists have been described to date and are currently available for the treatment of asthma. Molecular cloning of different CysLT receptor subtypes will certainly foster the development of new selective antagonists based on molecular modelling studies.