The mechanisms of chronic obstructive pulmonary disease exacerbation are complex. Respiratory viruses (in particular rhinovirus) and bacteria play a major role in the cause of these events. A distinct group of patients seems susceptible to frequent exacerbations, irrespective of disease severity, and this phenotype is stable over time. Many current therapeutic strategies help reduce exacerbation frequency. Further work is required to develop novel anti-inflammatory therapies for exacerbation prevention and treatment. This article focuses on the cause of chronic obstructive pulmonary disease exacerbations, and the current preventative and acute interventions available.