Pelvic inflammatory disease, the infection and inflammation of the female upper genital tract, is a common cause of infertility, chronic pain and ectopic pregnancy. Diagnosis and management are challenging, due largely to a polymicrobial etiology which is not fully delineated. Signs and symptoms of this syndrome vary widely, further complicating diagnosis and treatment. Due to the potential for serious sequelae, a low threshold for diagnosis and treatment is recommended. Since pelvic inflammatory disease has a multimicrobial etiology including Neisseria gonorrhoeae, Chlamydia trachomatis and anaerobic and mycoplasmal bacteria, treatment of pelvic inflammatory disease should be broad spectrum. Recent treatment trials have focused on shorter duration regimens such as azithromycin and monotherapies including ofloxacin, although data are sparse. Research comparing sequelae development by differing antimicrobial regimens is extremely limited, but will ultimately shape future treatment guidelines. Several promising short-duration and monotherapy antibiotic regimens should be evaluated in pelvic inflammatory disease treatment trials for compliance, microbiological and clinical cure, and reduction of subsequent adverse reproductive and gynecological morbidity.