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Many aspects of the care and underlying pathologies in patients suffering critical illness can detrimentally influence the normal healing processes of skin and soft tissues. Although a great diversity of pathologies exists, some aspects of the diseases and their treatments are common in critically ill patients. We aimed to identify some features, both common and specific, that could influence wound healing and the mechanisms by which they may do so.In this review, we first outline the biology of normal skin and muscle healing and then explore how critical illness may influence the normal healing cascade.The healing of skin and skeletal muscle in critical illness is influenced by both underlying disease processes and the intensive care environment. Local and systemic factors can contribute to impaired healing, with the potential to prolong functional disability and increase the likelihood of wound complications. The frequency and number of soft tissue injuries derived from accidental injury, surgical intervention, and the need for invasive monitoring and therapies in the intensive care unit setting are likely to compromise the innate immunity and potentially further jeopardize the patient’s ability to heal. Alterations in coagulation, tissue perfusion, inflammation, immune functioning, metabolism, nutrition, and drug therapies will influence healing responses by modifying the biological responses to tissue disruption. Locally, wound contamination, sepsis, tissue hypoxia, edema, and excessive or prolonged local pressure all have the potential to compromise soft tissue healing. One or more of these factors may be present at any time.The skin and soft tissues are vulnerable to both injury and compromised healing when a patient is critically ill and exposed to a critical care environment. The identification of risk factors may aid in forming and modifying treatment strategies when caring for the critically ill patient with soft tissue injuries.