Monomeric G-proteins, also referred to as small GTPases, function as biological hubs being activated by extracellular stimuli and regulate downstream signalling events, which result in different cellular responses. The importance of these mechanisms is mirrored by the fact that several pathological conditions, including allergic asthma, are associated with derailed GTPases signalling. For this reason attention has been focused on the role of monomeric G-proteins and their effectors in airway (patho)physiology. In this article we review our current knowledge on the regulation and functions of Ras and Rho GTPase signalling under physiological and pathophysiological conditions in the pulmonary system. Based on recent findings concerning novel regulatory proteins for Ras family members, we further discuss potential future directions for therapeutical interventions in asthma.