The threat of increasing multidrug-resistant infections (MDRI) is becoming a hot topic worldwide due to the potential risks in terms of global infections control and associated morbidity and mortality. Many potential reasons for this continuous increase of MDRI have been suggested and numerous projects are currently ongoing, which aim to investigate and stem this problem. In this review, MDRI has been analyzed in the context of the most relevant acute and chronic respiratory diseases, in order to provide an overall perspective of the topic and to identify future strategies of MDRI prevention or control in respiratory medicine. Mycobacterial infections were not considered, due to the large extent of this topic.