HIV is the ethiological agent of the Acquired Immunodeficiency Syndrome (AIDS). HIV infects mostly CD4+ immune cells, such as T lymphocytes, mononuclear phagocytes and myeloid dendritic cells and induces a progressive and deadly state of immunodeficiency if untreated with potent combinations of antiretroviral agents. The immunodeficient status of the host allows the development of several opportunistic infections as well as “opportunistic” tumors such as Kaposis’ sarcoma and B cell lymphomas. In addition, the ability of HIV-1 infected immune cells to localize in various tissues leads to tissue specific HIV-associated pathology, such as AIDS dementia, interstitial lung disease, nephropathy, enteropathy, and wasting syndrome. Of note, all these processes involve the upregulation or modulation of cytokines, soluble factors that regulate the immune responses and inflammation in addition to hematopoiesis. Due to space limitation and to the extent of informations about HIV and cytokines, this chapter will not discuss topics such as interactions between intracellular signalings by cytokines and HIV or the effect of the single viral proteins, such as gp120 Env, Tat and Nef, for which updated reviews/book chapters are available. In this chapter, we describe the general activities of cytokines and their role in modulating HIV infection, both in vitro and in vivo, animal models and human tissues such as gut and lymphoid tissue, and finally ways to which cytokines have been used as immunotherapy, either alone or in combination with anti-retrovirals.