Macrophages play a central role in the pathogenesis of atherosclerosis and are also a host for a number of viruses, most importantly, HIV. Many viruses, including HIV, require cholesterol for their replication and as a structural element. Cholesterol also plays a pivotal role in innate antiviral immune responses. Although impairing innate immune response by increasing cell cholesterol content may be a deliberate strategy used by a pathogen to improve its infectivity, enhancing the risk of atherosclerosis is likely a byproduct. Consistent association between HIV infection and elevated risk of atherosclerosis suggested a connection between virus-induced changes in cholesterol metabolism and atherogenesis, but the mechanisms of such connection have not been identified. We describe in this review various mechanisms enabling viruses to exploit macrophage pathways of cholesterol metabolism, thus diverting cholesterol for a purpose of increasing viral replication and/or for altering innate immune responses. To alter the cellular cholesterol content, viruses "hijack" the pathways responsible for maintaining intracellular cholesterol metabolism. The damage to these pathways by viral infection may result in the inability of macrophages to control cholesterol accumulation and may lead to formation of foam cells, a characteristic feature of atherosclerosis. Further elucidation of the mechanisms connecting viral infection and macrophage cholesterol metabolism may be fruitful for developing approaches to treatment of atherosclerosis and viral diseases.