Asthma, a disease that affects nearly 15% of the world's population, is characterised by lung inflammation and reversible airway obstruction, which leads to wheezing and dyspnoea. Asthma is a prototype for allergic processes initiated by tissue inflammatory leukocytes, such as mast cells, whose secreted mediators recruit lymphocytes and eosinophils to the lung parenchyma. Signals transmitted through G-protein-coupled receptors (GPCRs) contribute to both the development and perpetuation of allergic processes, and pharmacological agents that block or stimulate GPCR action have been a mainstay of allergic disease therapy. Despite the widespread use of GPCR-targeted agents, little is understood about intracellular regulation of G protein pathways in immune cells. Regulators of G protein signalling (RGS proteins) enhance G protein deactivation and may contribute to the specificity and precision characteristic of GPCR signalling pathways. This review discusses the emerging functions of RGS proteins in immune processes and inflammatory states such as asthma, and their potential value as therapeutic targets for the treatment of allergic disease.