Summary: Despite the introduction of inhaled steroids, long acting beta-mimetics, anti-cholinergic, anti-leukotrienes in asthma treatment, still some patients are not adequately controlled. Some of them fulfilled the definition of severe asthma, part of them has some other issues creating difficulties in asthma control. This leads to creating new biological agents and high doses of steroid/long acting betamimetics superfine combinations. This review is focused on practical approach to difficult to treat asthma treatment.