Tremendous progress has been made in the treatment of patients with asthma during the past decades. Whereas 30 years ago patients suffering with acute asthma attacks were admitted to the emergency department several times a day, today this has been reduced to a couple of patients a year. Treatment with inhaled corticosteroids (ICS) in the first instance, followed by the use of combination therapy with ICS and long-acting ß-agonists later on has greatly improved the long-term prognosis of asthma patients. Nevertheless, there are a number of patients that are not well controlled even with a high-dose combination therapy. Near fatal asthma attacks still occur and asthma mortality, although low, is still present. Difficult-to-treat asthma has been recognised as the severe form of the "other" asthma entities in the past. However, the understanding of the pathophysiology of this kind of asthma has been better understood during the last few years.