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Defining the nature of the association between chronic obstructive pulmonary disease (COPD) and other chronic conditions is of primary importance to improve the health status of COPD patients through the optimal care of comorbidities. We aimed at providing a reasoned guide to understand, recognize and treat comorbidity of COPD with the perspective of shifting from comorbidity to multimorbidity.Select comorbidities, such as atherosclerotic disease, depression, chronic kidney disease, cognitive impairment, obstructive sleep apnea syndrome, lung cancer, osteoporosis, diabetes, heart failure, sarcopenia, aortic aneurysm, arrhythmias and pulmonary embolism are highly prevalent among older COPD patients. Several concerns may affect the management of older COPD patients with comorbidity (e.g. the use of β-blockers in patients with COPD and cardiovascular diseases or concerns about the cardiovascular safety of inhaled COPD drugs).Evidence suggests that systemic inflammation may be the link between COPD and comorbidities, but this issue is still debated. Whatever the mechanism underlying comorbidities in COPD may be, it has an important clinical, prognostic and therapeutic impact. Nevertheless, clinical practice guidelines do not take into account comorbidities in their recommendations. Additionally, clinical trials investigating COPD treatment in the context of multimorbidity and considering geriatric outcomes are also distinctly lacking.