Severe refractory asthma is a heterogeneous condition with different patterns of severity and different reasons for loss of asthma control. The three main patterns include asthma with frequent exacerbations, asthma with irreversible airway obstruction, and asthma with reduced sensitivity or resistance to corticosteroids. Each of these patterns has distinct risk factors. The assessment of patients with severe asthma requires a systematic, diagnostic and management protocol. The majority of patients will benefit from thorough analysis and treatment of aggravating factors. In some patients with severe refractory asthma, in particular those with concomitant chronic rhinosinusitis, long-term administration of systemic corticosteroids may be necessary. In these patients all efforts should be directed towards reducing the dose of corticosteroids as much as possible. Although several corticosteroid-sparing agents and immunosuppressants have been proposed in the literature, none of these has gained complete acceptance in clinical practice, either because of limited efficacy or unacceptable adverse effects. Novel potent anti-inflammatory therapies aimed at reducing the need for systemic corticosteroids in patients with severe, refractory asthma are urgently needed.