HIV-positive individuals are at increased risk for cardiovascular disease due to complex interactions between the increased incidence of traditional cardiovascular risk factors and HIV and antiretroviral-associated inflammation and dyslipidemia. Increasing evidence suggests that a number of important co-pathogens, including cytomegalovirus, hepatitis C virus, and periodontal disease, are likely to also be contributing. Mechanisms such as molecular mimicry and modification of lipids play a role; however, induction of systemic inflammation is the likely key pathogenic link by which this occurs. Treatments to reduce the presence of infection, such as antibiotics, antivirals, or dental hygiene, show potential as modifiers of cardiovascular risk in HIV-positive individuals. This review will discuss the evidence regarding the contribution of these key co-pathogens, Chlamydia pneumoniae, cytomegalovirus, and hepatitis C virus, to cardiovascular risk in HIV-positive individuals. It will also review the roles that inflammation, microbial translocation, and periodontal infection play in promoting cardiovascular disease. The potential cardiovascular benefits of treating these infections with antimicrobials (such as valganciclovir) or improvements in dental hygiene (in the setting of periodontal disease) will be explored. As the life expectancy of HIV-positive individuals increases and the HIV-positive population thus ages, reducing the impact of age-related comorbidities, and particularly cardiovascular disease, will be of increasing importance at both an individual and population level.