Lentiviruses have adapted several strategies to avoid complement-mediated lysis. Thus, interaction of HIV or SIVmac with complement proteins and the subsequent binding to complement receptor (CR) positive cells, leads to significant enhancement of infection. In addition, the trapping of viral antigens and intact infectious viruses on follicular dendritic cells in the lymphatic tissue is, in the case of HIV, strongly dependent on complement. In contrast, natural hosts of primate lentiviruses such as African green monkeys, Sooty mangabeys or Chimpanzees are resistant to the development of clinical AIDS despite persistent replication of SIV. In the present review interactions of lentiviruses with complement in different primate species and the possible consequences of such interactions for the progression to AIDS in different hosts are discussed.