Patients presenting to the emergency department (ED) or clinic with acute exacerbation of asthma (AEA) can be very challenging varying in both severity and response to therapy. High-dose, frequent or continuous nebulized short-acting beta2 agonist (SABA) therapy that can be combined with a short-acting muscarinic antagonist (SAMA) is the backbone of treatment. When patients do not rapidly clinically respond to SABA/SAMA inhalation, the early use of oral or parenteral corticosteroids should be considered and has been shown to impact the immediate need for ICU admission or even the need for hospital admission. Adjunctive therapies such as the use of intravenous magnesium and helium/oxygen combination gas for inhalation and for driving a nebulizer to deliver a SABA and or SAMA should be considered and are best used early in the treatment plan if they are likely to impact the patients' clinical course. The use of other agents such as theophylline, leukotriene modifiers, inhaled corticosteroids, long-acting beta2 agonist, and long-acting muscarinic antagonist currently does not play a major role in the immediate treatment of AEA in the clinic or the ED but is an important therapeutic option for physicians to be aware of and to consider initiating at the time of discharge from clinic, hospital, or ED to reduce later clinical worsening and readmission to the ED and hospital. A comprehensive summary is provided of the currently available respiratory pharmaceuticals approved for asthma and other airway syndromes. Clinicians must be prepared to use the entire spectrum of medications available for the treatment of acute asthma exacerbations and the agents that should be initiated to prevent worsening or additional exacerbations. They need to be familiar with the major potential drug toxicities associated with their use.