Marginal variation in performance produces highly significant implications at the elite athletic level participating in endurance sport. Athletic performance is dependent upon the optimisation of a number of physiological determinants including several respiratory limiting factors suggested to affect exercise performance negatively. However, in elite athletes, the capacity of the cardiovascular and muscular-skeletal systems can exceed the structural and functional capacities of the lung and airways. The normal responses of the airways during exercise are relaxation of the bronchial smooth muscle as a result of withdrawn parasympathetic tone, increases in tidal end inspiratory lung volumes, activation of upper airway dilator skeletal muscles and a continuous recruitment of expiratory muscles with increasing work rate or intensity. However, in a significant proportion of the elite athletes (40%) exercise triggers a constriction in the smooth muscle surrounding the airways. The diagnosis of exercise-induced bronchoconstriction (EIB), also called exercise-induced asthma (EIA), is a complex process. The impact of untreated or mistreated EIB on performance is unknown. During the summer Olympic Games of 2006 and 2010, the use of beta2-agonists was between 7.1 and 7.7%, with a higher use among endurance athletes of 19.1 and 17.3% in Olympic swimmers and cyclists, respectively. A substantial amount of research has been conducted investigating the effects of treatment on EIB and asthma over the years. EIB can be prevented with inhaled corticosteroids (ICS), either alone with a short-acting beta2-agonist (SABA) as rescuer, or in combination with a long-acting beta2-agonist (LABA). Given the high prevalence of asthma and exercise-induced bronchoconstriction among elite athletes, there is a high use of beta2-agonists. It is still debated whether inhaled beta2-agonists are performance enhancing. Notably, Olympic asthmatic athletes that use inhaled beta2-agonists win more medals than their non-asthmatic counterparts. While it has been speculated that this may reflect that asthmatic athletes are better prepared at training and in competition, recent studies suggest that high dose inhalation of beta2-agonist, even within the current anti-doping regulations, is performance enhancing. Performance enhancing effects of beta2-agonist are a well-known phenomenon when administered in prohibited oral doses, which may be attributed to the systemic effects that beta2-agonists elicit in various tissue. Pharmacokinetic data indicate that the systemic bioavailability of inhaled beta2-agonists is higher than oral, why it is likely that inhaled beta2-agonists possesses same systemic effect as oral. The systemic effects of beta2-agonists that may be relevant for performance include enhanced ion handling and increased rate of glycogenolysis and glycolysis in skeletal muscle. The aim of this lecture is to present the most recent data on beta2-agonists in relation to performance, muscle physiology and doping. Furthermore, to discuss whether the 2015 World Anti-doping Agency’s regulation of beta2-agonists is adequate to ensure fair competition and to detect supratherapeutic misuse of beta2-agonists.