Severe and difficult-to-treat asthma patients have impaired health status and account for over half of the cost of the disease and probably all of its mortality. Guideline-based treatment for these refractory asthma patients includes high doses of inhaled steroids and long acting beta2-agonists (LABA) as well as additional medication such as theophylline, oral steroids and leukotriene-antagonists. However, management regimens are rarely successful in these patients, the treating physicians are often at a loss and there are still many areas of uncertainty regarding steroid-responsiveness, safety issues and maximal dosing of inhaled corticosteroids (ICS) and bronchodilators and possible differences between ICS preparations. Furthermore, there are many other classes of medication that have been or are currently tested in severe asthma: Anti - Immunoglobulin E (IgE) seems to have a good clinical effect while results on anti - Interleukin 5 (IL-5) are less promising and anti - tumor necrosis factor alpha (TNFalpha) treatment is currently being tested in controlled studies. Other steroid sparing drugs (cyclosporine, tacrolimus, methotrexate, gold) have been used but results are unsatisfactory and side-effects are notable so steroids remain the cornerstone of severe asthma treatment. The addition of macrolides is beneficial in many cases and this is in step with the evidence of chronic chlamydia infection in severe asthma. Although there are case reports supporting the use of Immunoglobulin G (IgG), there are no controlled studies supporting this type of treatment. In this report, the authors review the various issues of guideline based therapy but also new approaches that include anti-IgE antibodies, anti-cytokines (anti-IL-5, anti-IL9, anti-TNF).