Exhaled breath condensate (EBC) collection is a noninvasive means of obtaining lower respiratory tract samples that can be safely used to detect inflammatory markers and a variety of molecules. Interestingly, the concentration of these biomarkers in EBC is influenced by the presence of lung diseases and may be modulated by therapeutic interventions. Despite a number of technical limitations, EBC has multiple advantages, mainly related to its noninvasiveness, that make it especially attractive for use in critically ill and mechanically ventilated patients. However, although evidence on the use of EBC is increasing rapidly, only few studies including critically ill and mechanically ventilated patients have been published to date; most investigations have focused on EBC acidity, nitric oxide-related compounds, and markers of oxidative stress. Further research is needed to establish the possible role of EBC in the general management of critically ill patients in the future. The aim of this review was to analyze the current knowledge regarding EBC use in critically ill mechanically ventilated patients.