Several years ago, omalizumab became commercially available for the treatment of severe asthma. It remains the only monoclonal antibody to be marketed for this purpose. Since then, many studies have been published endorsing its efficacy and effectiveness. Concomitantly, evidence of an overlap between atopic and non-atopic severe asthma has emerged. However, there also appears to be some disagreement regarding the value of omalizumab in the management of non-atopic disease, as some studies have failed to show any benefit in these patients. The recent literature has also sought to identify appropriate prognostic biomarkers for the use of omalizumab, other than immunoglobulin (IgE) levels. This article briefly summarizes the evolution of asthma treatment, the pathophysiology of the condition, and the method of action of omalizumab. The author describes the controlled and uncontrolled studies (also named "real-life studies") published in adult and pediatric populations in different countries and expresses his view on the current place of the drug in the management of severe allergic asthma. He offers a personal perspective on the recent evidence for the use of omalizumab in non-atopic patients, highlighting the implications for current clinical practice and the gaps in our knowledge. The author justifies his belief that omalizumab is not only an IgE-blocking drug and should be considered as a disease-modifying therapy because of its multiple effects on different biologic pathways. Finally, some areas for future research are indicated.