Asthma is a chronic inflammatory disorder of the respiratory system characterised by recurrent “reversible” obstruction of the airwflow in the airway. Various agents have been used in the treatment of asthma out of which inhaled beta-2 agonists have been mainstay of bronchodilator therapy of asthma for more than 40 years. Short-acting beta-2 agonists are still recommended for relieving the acute episode of bronchoconstriction. Long-acting beta-2 agonists (LABAs), alongwith inhaled corticosteroides are used as a first line anti-inflammatory therapy. The recent evidence suggested that the ability of short-acting and long-acting beta-2 agonists to protect the airways against bronchoconstrictor stimuli and to promote bronchodilatation may be partially lost with time following long-term use. The long-term use of beta-2 agonist is associated with an increased incidence of asthma exacerbations and other markers of morbidity and mortality. In this article, we try to address some of the current controversies as well as propose various mechanisms behind beta-2 agonist induced morbidity and mortality in asthmatic patients. On the basis of this article, we recommended that clinicians have to refine the use of beta-2 agonists in asthma management guidelines to avoid the beta-2 agonists induced asthma exacerbations.