Despite several techniques, such as non-invasive ventilation (NIV), have improved the outcome of the acute exacerbation, COPD remains affected by poor prognosis in the medium and long term. Moreover, the task of predicting prognosis remains a major challenge for respiratory physicians. In order to overcome this limitation, several indexes have been proposed to assess the COPD patient in his/her complexity. The rationale is that, by using numerical indexes physicians may improve their clinical judgment to tailor and share therapeutical choices, i.e. referring the patient for surgery or lung transplantation. On this ground, Almagro et al. recently proposed the CODEX index, as the latest evolution of the BODE through the BODEx (which takes into account exacerbations), by adding the evaluation of comorbidity to the severity of dyspnoea, airway obstruction and history of exacerbations. As afore mentioned, treatment of COPD with respiratory acidosis has been revolutionized by the use of NIV, by reducing the need for intubation and in-hospital mortality of patients with severe COPD exacerbations. Nowadays, new promising techniques, such as minimally invasive extracorporeal devices, may hasten the clearance of carbon dioxide and reduce the work of breathing and the need for ventilation of COPD patients. These techniques still lack of randomized controlled studies; however, the approach of extracorporeal CO2 removal has the potential to further improve the prognosis of severe exacerbation of COPD patients. In this paper we discuss the prognostic evaluation of patients affected by COPD through the evolution of dedicated indexes, which mirror the focus of current research on the disease.