Examination of the placenta provides a unique opportunity to explore and understand the intrauterine environment, as well as providing a record of events that may be associated with adverse pregnancy outcomes, one of the most devastating of which is central nervous system (CNS) injury. A number of placental lesions have been described in association with various forms of neurologic injury. They can be divided into four major categories: sentinel events, inflammatory lesions, vascular lesions, and "biomarker" lesions, which are not themselves causative, but are often found in association with other lesions that are causative. The purpose of this review is to outline these placental lesions and summarize the types of CNS injury that have been described in association with each. Finally, one of the most important of all risk factors for CNS injury is the finding of multiple independent placental lesions. The effects of these lesions may be synergistic, particularly when metachronous, with an earlier lesion leaving the CNS more vulnerable to the effects of a later lesion.