Current guidelines recommend inhaled steroids as the first line control medication in the treatment of asthma. However, many patients particularly with airway obstruction need bronchodilators either as a symptom reliever or control medication to provide relaxation of bronchiolar smooth muscles. Both short acting and long acting beta-2 agonists (SABA and LABA) are of particular importance among the bronchodilators used in asthma. Despite their well-known benefits, in the recent years, a growing body of publications has been published on the safety of LABAs. However, the increased risk reported to be related to LABA monotherapy was not observed in patients receiving inhaled corticosteroid as the standard treatment in combination with LABA. The benefits of adding LABAs to inhaled corticosteroid have been thoroughly documented, while the risks, including asthma mortality, are currently under debate. Pharmacogenetic advancements drew attention to a potential genetic explanation for certain side effects of these medications whose efficacy and safety have been proven in several studies. In conclusion, LABAs are effective in relieving symptoms and improving lung functions and safe when combined with inhaled corticosteroid in asthma; however, LABA monotherapy should never be administered in the absence of inhaled corticosteroid treatment. Asthma patients that lack control of disease despite adequate doses of inhaled corticosteroids need addition of a regular bronchodilator to their treatment regimen.