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Localized radiation injuries account for the vast majority of accidental radiation exposures and mainly occur due to direct handling of highly intense radioactive sources. Their clinical course and severity mainly depend on the type of radiation, radiation source, dose and dose rate, duration of exposure, dose distribution, and location and size of the area exposed. Local injuries appear as skin injuries; however, they may involve radiation damage to other organs and tissues. Local injuries evolve slowly over time and clinical signs and symptoms usually take days to weeks to manifest. Although in most cases not life threatening, their delayed effects may result in serious impairments. Standardized therapeutic protocols and evidence-based approaches for the management of local injuries do not exist yet. Local injuries should therefore be treated symptomatically. The two main approaches comprise conservative and surgical treatment. Conservative methods focus on pain control, reduction of inflammation, prevention of infection and of further vasculature insult, improvement of circulation, healing acceleration, wound cleaning, and minimizing fibrosis. Surgical treatment and plastic remodeling of anatomic structures may be required. During recent years, significant progress has been made in the management of local injuries. There is increasing evidence that injections of human mesenchymal stem cells may be a promising therapeutic approach in the treatment of cutaneous radiation reactions. A consistent follow-up of radiation patients keeping in mind the possible onset of late radiation effects will contribute to the comprehensive understanding of the pathophysiology of the radiation reaction which is crucial to establish evidence-based diagnostic and therapeutic strategies.