Mucocutaneous involvement of infectious diseases are commonly observed and in a large variety of presentations. Microbes interfere by entering directly into the mucous membrane or cutaneous envelope or by systemic or loco-regional dissemination. Skin as a superficial, accessible and physical envelope is proposed in order to emphasize the importance of clinical accuracy and laboratory tests performance in such remarkable organ. Visual access by the patient himself or the physician allows an early diagnosis and close follow-up without any invasive diagnosis tool. In other part, simple and painless samples may lead to determinant conclusion and a quick cutaneous tissue biopsy may safe your patient. Host local and general immunity is primary for microbe multiplication or pathogenecity developpement and few key-points about skin proper immunity and relations with general immunity are noted. HIV infection is a perfect illustration for all these considerations about skin role. The virus directly induces cutaneous troubles but most of the time the associated pathologies are secondary to immune imbalance. Opportunistic infections are unfortunately the occasion to discover new microbes or exceptional clinical presentation of known infectious agents. The beneficial difference between the pre HAART era and early and late HAART eras is very clear when considering cutaneous disturbances in HIV patients. Although this dramatic health condition improvement, the focus will be done on considering cutaneous adverse drug reactions and non infectious co-morbidities including subcutaneous modifications in adipose tissue and lipodystrophy syndrome. Moreover, many cancer occurences increase including skin cancers associated or not with Human Papilloma virus infection. In 2011 and later, the main challenges in dermatology will be to continue to fight against all sexually transmitted diseases, to help people living with HIV to restore their body image destroyed by the chronic disease and the social stigmatization, then better understand the pathophysiology of skin tumors in order to optimize their prevention and treatment.