Respiratory infections are a major cause of global mortality and morbidity. In recent years, an increased incidence of multidrug-resistant (MDR) Gram-negative bacteria (GNB) has been described. Microorganisms such as Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae or Acinetobacter baumannii have been identified as causative pathogens of different respiratory tract infections. Several studies have detected MDR-GNB in patients with community-acquired and nosocomial pneumonia. Furthermore, MDR-GNB have also been isolated in patients with chronic obstructive pulmonary disease and bronchiectasis having acute or chronic bronchial infection. Prevalence varies depending on the geographical area but MDR-GNB has been reported in the Asia-Pacific region, Europe and the United States, reaching rates of 70% in hospital-acquired infection. The presence of MDR-GNB has been related to poor clinical outcomes, including increased mortality, although data regarding this relationship are limited. This is probably linked to inappropriate selection of empiric antibiotic treatment; this poses a threat of widespread resistance. GNB antibiotic resistance and the absence of new antibiotics are a major concern given limited treatment options; an aspect that deserves future research. We review current literature, highlight prevalence of MDR-GNB in different respiratory infections and explore their impact on clinical outcomes.