We hypothesize that there exists a substantial and growing group of “persistently critically ill” patients who appear to be intensive care unit-dependent because of a cascade of critical illnesses rather than their original ICU admitting diagnosis. These persistently critically ill patients are those who remain in the ICU because of ongoing complications of care that continue after their reason for admission has been treated and is no longer active. We believe such patients can be distinguished from patients currently labeled as “chronic critical illness” or “prolonged mechanical ventilation”. We further believe that their primary problem is not simply failure to wean from mechanical ventilation due to muscle weakness and impaired gas exchange. We outline a program of clinician consultation, epidemiological research, consensus conference and validation to develop a useful definition of persistent critical illness, with the aim of supporting investigations in preventing persistence, and improving the care of patients so affected.