Due to the worldwide AIDS pandemic, HIV-1 has become the major factor for central nervous system (CNS) diseases. Two major disorders of the CNS caused by HIV-1 have been described, a meningoencephalitis which occurs in 30-50% of patients early after infection and the AIDS dementia complex (ADC, also known as HIV-associated dementia) which is characterized by a predominantly subcortical dementia. The pathophysiology of these clinical syndromes still remains an enigma. However, since monocytes/macrophages may represent the major place of virus replication in the CNS, a hematogenous invasion of HIV-1 into the brain may be crucial to the neuropathogenesis of ADC. One of the most valuable animal models for the study of neuro-AIDS is the infection of macaque monkeys with the simian immunodeficiency virus (SIV). In about 50% of infected rhesus monkeys with an AIDS-like disease, neuropathological lesions similar to ADC in men have been observed. This animal model contributes to our understanding of the mechanisms of viral neuroinvasion early after infection and in the development of neurological disease. In this review we will summarize the state of the art and will focus on further questions concerning the neuropathogenesis of HIV/SIV.