Asthma is a chronic inflammatory multifactorial disorder of the airways characterized by the involvement of immune cells and mediators in its onset and maintenance. Traditional therapeutic strategies have been unsatisfactory in controlling the underlying pathology, especially in the more severe states. Hence in the last couple of decades, new biological approaches targeting molecular mediators have been developed. In this narrative review we examine biological agents currently available for the management of severe asthma, focusing our attention on their clinical application, pros and cons, and in particular on gaps regarding the use of these agents. The most well-known and used biologic agent in clinical practice is omalizumab, though there is emerging evidence for mepolizumab too. The future of these biological therapies is to broaden our knowledge of their practical use and ascertain predictive biomarkers, or define an algorithm, useful in the optimal application of these 'biological weapons'.