The skin has several physical, chemical and immunological properties which help to protect the internal organs. In addition, there is a physiological colonisation of commensal microbes which help to suppress the expansion of pathogenic germs on the skin. Genetic or acquired immunodeficiency will have an impact to these factors. Drug induced immunodeficiency is common in organ transplanted patients with the aim to prevent organ rejection. HIV infection most commonly leads without therapy to marked immune suppression. Such patients with prolonged immunodeficiency often develop atypical manifestation of mucocutaneous infections. Therefore such patients should be biopsied liberally and besides the conventional histology a part of the biopsied tissue should be used for microbiological cultures. In addition to acute infections of the skin, long-term effects of oncogenic viruses have to be taken in account which can lead to epithelial cancers (HPV), Kaposi sarcomas (HHV8) and lymphomas (EBV). There are mucocutaneous markers for immunosuppression such as oral hairy leukoplakia, which are commonly seen in AIDS patients but may also be observed in otherwise chronically immune suppressed patients. This work gives an overview to the pathophysiology of skin protection and describes typical mucocutaneous infections in immune suppressed patients.