Severe asthmatics often exhibit poor control despite high doses of inhaled corticosteroids with or without systemic corticosteroids and suffer from persistent symptoms and/or recurrent exacerbations. Five to ten percentage of the asthmatic population falls within this category. Patients with severe asthma are a heterogeneous group and should be investigated to confirm the diagnosis, identify comorbidities, exclude alternative diagnoses, together with an evaluation of treatment adherence and side-effects from medications. Optimization of asthma medications and monitoring the control and pattern of asthma usually takes place over a period of 6 months. In patients with confirmed severe refractory asthma, further evaluation is needed in terms of detailed lung function, of airway and lung structure using high resolution computed tomographic scanning, and of airway inflammatory processes and biomarkers using induced sputum or bronchial biopsies. Patients with severe asthma are best investigated and managed with a multidisciplinary team. Severe asthma consists of different phenotypes that need defining. Investigation of severe asthma should bring into the open the various characteristics of the disease that could point to particular phenotype. Inclusion of investigations based on transcriptomics and proteomics should expand, improve classification and understanding of severe asthma, with the ultimate hope of finding more effective treatments and a step towards personalized medicine.