Ain manifestations primarily associated with the retroviral infection itself still remains under investigation. The focus of this review is to highlight the immunological phenomena that occur in the skin of HIV-1-seropositive patients, which ultimately lead to skin disorders, such as seborrhoeic dermatitis, atopic dermatitis, psoriasis and eosinophilic folliculitis. Furthermore, we compile the latest data on how shifts in the cytokines milieu, impairments of the innate immune compartment, reactions to xenobiotics and autoimmunity are causative agents in HIV-1driven skin diseases. Additionally, we provide a thorough analysis of the small animal models currently used to study HIV-1-associated skin complications, centering on transgenic rodent models, which unfortunately, have not been able to fully unveil the role of HIV-1 genes in the pathogenesis of their primarily associated dermatological manifestations. Review More than 25 years have passed since the first reports on AIDS, and we are still unable to fully understand the complexity of this disease. Dermatologic disorders play a unique role in the HIV-1/AIDS spectrum, as almost all seropositive patients suffer from these debilitating and often disfiguring lesions [1]. Cutaneous disorders associated with HIV-1/AIDS undermine self-esteem and induce depression, conditions that put patients at high risk of suicide. Since the description of Kaposi’s sarcoma as an AIDSrelated condition, 56 other cutaneous disorders have been linked to HIV-1/AIDS [2]. Although the introduction of highly active antiretroviral therapy (HAART) significantly decreased the prevalence of opportunistic infections and Kaposi’s sarcoma, the prevalence of most inflammatory conditions primarily related to HIV-1 remains constant [3,4]. Nevertheless, while most of* Correspondence: [email protected] 6 TruBios Research Institute, Johns Hopkins University, MCC, Rockville, Maryland 20850, USA Full list of author information is available at the end of the articlethese dermatological manifestations directly associated with HIV-1/AIDS are currently considered as markers of disease progression, the pathogenesis of some of them is not completely understood yet [5]. Recent explanations about the pathogenesis of these disorders suggest that not only the decline in CD4+ T cell counts [6], but also the shift into a Th2 cytokine profile [7], the molecular mimicry [8] and the over-expression of superantigens/xenobiotics [9], play a decisive role in the development of dermatological lesions in the context of HIV-1 infection. Importantly, there is PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/27385778 still a lack of conclusive evidence linking HIV-1-associated gene products to the pathogenesis of primary dermatological disorders seen in AIDS patients. This fact derives from multiple factors that include: (1) the shortage on biosafety level 3 (BSL-3) facilities and BSL-3-trained individuals; (2) the expenses associated with non-human primate studies; and (3) the lack of small animal models to study this particular disease. In order to overcome the latter, many groups, including ours, have created transgenic rodent models (rat and mouse) for the study of?2011 Cedeno-Laurent et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any MK-571 (sodium salt)MedChemExpress MK-571 (sodium salt) medium, provided the original work is properly cited.Cedeno-Laurent e.