ABSTRACTDamage to the skin, subcutaneous tissues and blood vessels are among the most common health harms related to injecting drug use. From a limited range of early reports of injecting‐related skin and soft tissue damage there is now an increasing literature relating to new drugs, new contaminants and problems associated with unsafe injection practices. Clinical issues range from ubiquitous problems associated with repeated minor localised injection trauma to skin and soft tissue and infections around injection sites, to systemic blood infections and chronic vascular disease. The interplay of limited availability and access to sterile injecting equipment, poor injecting technique, compromised drug purity, drug toxicity and difficult personal and environmental conditions give rise to injection‐related health harms. This review of injecting‐related skin, soft tissue and vascular damage focuses on epidemiology and causation, clinical examination and investigation, treatment and prevention.