SIV infection of nonhuman primates is widely utilized as a powerful model of human AIDS. The major effort in this field has so far been oriented towards the induction of an AIDS like disease in the disease susceptible species with the aim to elucidate mechanisms of HIV/SIV induced disease. The fact that there exist disease resistant natural SIV infected host species offers a unique opportunity for comparative studies aimed at not only defining of those mechanisms that may be critical in the development of disease but also the mechanisms that are important for the disease resistance in the natural host. The hallmark of pathogenic HIV and SIV infection is generalized immunosuppression due to both a loss and functional impairment of CD4+ T cells. This review summarizes currently available data on CD4+ T cell function in the naturally SIV infected sooty mangabey with potential implications of these characteristics for our understanding of the pathogenesis of SIV infection.