Asthma is an important chronic disease which imposes a huge financial pressure on medical health services. Acute attacks and referral to Emergency Department is a challenge. Many Environmental Factors influences asthma in addition to its hereditary basis. Asthma is the culprit of significant number of missing school and work days due to the disease restrictions. Many cross-sectional studies have confirmed increases in the incidence and prevalence of asthma over the past 2 to 3 decades. Almost 25% of annual Emergency Departments visits are related to asthma. Asthma especially in acute setting medical management is a research attraction. Novel therapeutic strategy results are challenging and complex, a lot of new treatment is under investigation. Traditional standard medications in the disease acute setting consist of Oxygen administration, B2 adrenergic agonists, anticholinergics and corticosteroids depends on the severity of the attack. Current recommendations favor inhaled corticosteroids for all patients with mild persistent asthma or more severe asthma. Magnesium parenteral administration in severe asthma attacks improves airflow obstruction and decreases the need for hospital admission. Methylxanthines has no role in the acute attack medications because of their lack of demonstrated efficacy and increases in adverse events. An IV bolus dose of 0.2 milligram/kg of Ketamine followed by an infusion of 0.5 milligram/kg/h is sometimes used in status asthmaticus and may be beneficial. There is limited data regarding ketamine efficacy in treating severe asthma. Epinephrine can be given subcutaneously or intramuscular in adult in refractory life threatening situations. Terbutaline is an option for patients whom cannot tolerate inhaler treatments such as very severe attacks. IV β-agonist infusions offer no advantage over aerosolized or metered-dose inhaler–delivered agents and carry increased risk. Some studies state that leukotriene modifiers such as montelukast and zafirlukast may improve FEV1/PEFR when given during acute attack. Despite one trial with adjuvant IV montelukast for acute Asthma, there is no indication for the use of any of the leukotriene modifiers in the ED. antibiotics has no role in the management of uncomplicated acute asthma. Heliox can lower airway resistance as an adjunctive treatment of severe asthma, but does not reliably avert tracheal intubation and hospital admission and mortality. Analaysis Based on Heliox effect on Spirometeric and clinical improvement of acute asthma attack are controversial. One study data revealed Addition of nebulized furesmide to asthma standard treatment increases peak flow rate but it does not significantly affect FEV1, FVC or clinical score. These data were not concluding. Some research data suggest that lidocaine seems a novel promising agent for it’s off the label use in steroid dependent asthma. Inhaled lidocaine through its anti-inflammatory and direct smooth muscle relaxant action possesses a substantial role in the treatment of steroid dependent asthma. One study data showed a novel natriuretic peptide receptor-A acts as a bronchodilator and it can be a potential target for new asthma management. Tacrolimus acts as an immunosuppressor drug via inhibition of cytokine production and might be useful for the treatment of asthma and possibly other T cell suppressors do the same. Some Studies claim that Neurokinin antagonists may inhibits neurokinin A induced bronchoconstriction in asthma. Some researchers showed Thiazolidinediones such as troglitazone and rosiglitazone, in long term use, may have a broad anti-inflammatory effect and possibly beneficial as an asthma medication.There is a report of two cases, whose symptoms related to asthma had remitted during treatment with pioglitazone, but the objective data supporting improvement of asthma were not sufficient. Prostacycline analogs such as iluprost, possibly via production of IL-10 and Supression of TNF-a, can be effective in asthma improvement. Based on some results Heparin nebulize may possibly promote FEV1 as an asthma treatment, but the data were not concluding. Omalizumab, a recombinant humanized monoclonal anti-IgE antibody, selective inducible NO synthetase inhibitors and gene-directed therapies are another under evaluation asthma therapies that their efficacy have not been proved. There are significant controversies in the field of new introduced medications, suggesting for acute asthma treatment and a lot of ambivalences that should be answered. This is a long way to clarify the costs and benefits of the different under investigation drugs and the conflicts in the research results. More trials are needed to clarify a lot of questions to open more windows to the asthma acute attack treatment especially for the Emergency Departments.