Pelvic inflammatory disease (PID) is a substantial cause of reproductive morbidity in young women. A systematic review of the literature related to PID management was performed in preparation for the 2006 Centers for Disease Control and Prevention sexually transmitted diseases treatment guidelines. This search was conducted using PubMed and was limited to articles written in English and published between 1 January 2002 and 31 January 2005 that were related to PID treatment. Studies were evaluated for new data on PID with regard to site, route, and timing of antimicrobial administration; regimen adherence; experience in adolescents and women >35 years of age; coinfection with human immunodeficiency virus; and management of sex partners. Strong evidence suggests that neither site nor route of treatment administration affects the short- or long-term major outcome of women with mild or moderate clinical presentations. Data on these outcomes in women with more severe clinical presentations are inadequate to provide guidance as to the preferred agents or route of administration. Important contributions to the literature that impact the 2006 guidelines are described in this article.