New therapeutic options for severe asthma have recently emerged, mostly in the form of monoclonal antibodies ("biologicals") targeting relevant inflammatory pathways. Currently available agents target different aspects of "Type 2" immunity, and their indications often include overlapping patient groups. We present a round-table discussion that took place during the Annual Meeting of the Respiratory Effectiveness Group (REG), on the reasoning behind the use of different add-on medications for severe asthma, and crucially, on selection strategies. The proposed rational is based on current evidence, including real-life studies, as well as on the appreciation of the relevant complexities. Direct head-to-head comparisons of biologicals are lacking; therefore, algorithms for initial choice and potential switch between agents should be based on understanding the key characteristics of different options and the development of a clear plan with predefined targets and shared decision-making, in a structured way.