Although advances in intensive care have enabled more patients to survive an acute critical illness, they also have created a large and growing population of chronically critically ill patients with prolonged dependence on mechanical ventilation and other intensive care therapies. Chronic critical illness is a devastating condition: mortality exceeds that for most malignancies, and functional dependence persists for most survivors. Costs of treating the chronically critically ill in the United States already exceed $20 billion and are increasing. In this article, we describe the constellation of clinical features that characterize chronic critical illness. We discuss the outcomes of this condition including ventilator liberation, mortality, and physical and cognitive function, noting that comparisons among cohorts are complicated by variation in defining criteria and care settings. We also address burdens for families of the chronically critically ill and the difficulties they face in decision-making about continuation of intensive therapies. Epidemiology and resource utilization issues are reviewed to highlight the impact of chronic critical illness on our health care system. Finally, we summarize the best available evidence for managing chronic critical illness, including ventilator weaning, nutritional support, rehabilitation, and palliative care, and emphasize the importance of efforts to prevent the transition from acute to chronic critical illness. As steps forward for the field, we suggest a specific definition of chronic critical illness, advocate for the creation of a research network encompassing a broad range of venues for care, and highlight areas for future study of the comparative effectiveness of different treatment venues and approaches.