Chronic obstructive pulmonary disease (COPD) is defined by chronic airflow obstruction, but is presently considered as a complex, heterogeneous, and multicomponent disease in which comorbidities and extrapulmonary manifestations make important contributions to disease expression. COPD-related hospital readmission. In particular frequent intensive care unit (ICU) readmissions for exacerbations represent a major challenge and place a high burden on patient outcomes and health-related quality of life, as well as on the healthcare system.In this narrative review, we first address major and often undiagnosed comorbidities associated with COPD that could have an impact on hospital readmission after an index ICU admission for acute hypercapnic respiratory failure. Some guidance for treatment is discussed. Second, we present predictors of hospital and ICU readmission and discuss various strategies to reduce such events.There is a strong rationale to detect and treat major comorbidities early after index ICU admission for acute hypercapnic respiratory failure. It still remains unclear, however, if a comprehensive and holistic approach to comorbidities in frail patients surviving hypercapnic respiratory failure can efficiently reduce the readmission rate.