Women seropositive for human immunodeficiency virus type 1 (HIV-1) are at an increased risk for a number of adverse perinatal outcomes. Although efforts to reduce mother-to-child transmission of HIV (MTCT) remain a priority in resource-limited countries, HIV testing and treatment have led to steep declines in MTCT in well-resourced countries. Even so, HIV seropositive pregnant women in the United States continue to deliver a disproportionately high number of preterm and low birth weight infants. In this mini-review, we address the role of the placenta in such HIV-related perinatal sequelae. We posit that adverse perinatal outcomes may result from two mutually non-exclusive routes: (1) HIV infection of the placenta proper, potentially leading to impaired maternal-fetal exchange; and (2) infection of the maternal decidual microenvironment, possibly disrupting normal placental implantation and development. Further research into the relationship between HIV-1 infection and placental pathology may lead to the development of novel strategies to improve birth outcomes among HIV-1 seropositive parturients.