Alpha1-adrenoceptors are one of three subfamilies of receptors (alpha1, alpha2, beta) mediating responses to adrenaline and noradrenaline. Three alpha1-adrenoceptor subtypes are known (alpha1A, alpha1B, alpha1D) which are all members of the G protein coupled receptor family, and splice variants have been reported in the C-terminus of the alpha1A. They are expressed in many tissues, particularly smooth muscle where they mediate contraction. Certain subtype-selective agonists and antagonists are now available, and alpha1A-adrenoceptor selective antagonists are used to treat benign prostatic hypertrophy. All subtypes activate phospholipase C through the G(q/11) family of G proteins, release stored Ca2+, and activate protein kinase C, although with significant differences in coupling efficiency (alpha1A > alpha1B > alpha1D). Other second messenger pathways are also activated by these receptors, including Ca2+ influx, arachidonic acid release, and phospholipase D. Alpha1-adrenoceptors also activate mitogen-activated protein kinase pathways in many cells, and some of these responses are independent of Ca2+ and protein kinase C but involve small G proteins and tyrosine kinases. Direct interactions of alpha1-adrenoceptors with proteins other than G proteins have not yet been reported, however there is a consensus binding motif for the immediate early gene Homer in the C-terminal tail of the alpha1D subtype. Current research is focused on discovering new subtype-selective drugs, identifying non-traditional signaling pathways activated by these receptors, clarifying how multiple signals are integrated, and identifying proteins interacting directly with the receptors to influence their functions.