Although CCI is defined as prolonged ventilatory failure with tracheotomy stemming from preceding critical illness, the contention that multisystem debilities impact on most CCI patients' care and recovery is a central thesis of this volume. Perhaps reflecting the combined debilities inherent in CCI, infectious complications take their toll in morbidity, mortality, and persistent ventilatory insufficiency. Enhanced susceptibility to infection results from a potent admixture of barrier breakdown, exposure to virulent and resistant nosocomial pathogens, and postulated "immune exhaustion" that stems from the combined impact of comorbidities and the sequellae of critical illness. Strategies to improve outcome in CCI-related infection include standard measures of support especially nutrition, reducing environmental inoculum through pulmonary hygiene measures, skin care, and limiting barrier breaches, and appropriate antimicrobials directed at likely pathogens. Future stratification of patient risk on the basis of immune phenotype or genotype and potential immunomodulatory prophylaxis may be around the corner, as new prospects in the pharmaceutical armamentarium are presently undergoing testing.