The widespread access to antiretroviral treatment during the past decades has transformed HIV infection from a lethal disease to a chronic condition, in which the relative burden of non-AIDS-related chronic disorders such as cardiovascular disease, malignancy, renal, liver, and bone disease has increased. The adjusted relative risk for myocardial infarction is reported to be around 2-fold compared to that of the general population, which over time is likely to translate into increased absolute risk in an aging population. Thus, delineating potentially HIV-specific pathogenetic mechanisms is crucial in order to tailor novel strategies for prophylaxis and treatment. This review will focus on advances in the field that possibly link HIV-induced alterations of the gut mucosa and consequent microbial translocation to cardiometabolic risk factors in HIV infection. Recent work suggests that markers of microbial translocation are closely associated with several cardiovascular risk factors such as dyslipidemia, insulin resistance, hypertension, coagulation abnormalities, endothelial dysfunction, and carotid atherosclerosis. Future studies should investigate whether associations between microbial translocation and cardiovascular risk factors will translate into increased risk of acute events, and whether strategies to target gut microbiota and microbial translocation might reduce such a risk.