Pelvic inflammatory disease (PID) is a common reproductive health disorder among women of reproductive age. The treatment of PID has slowly evolved, reflecting changing antibiotic susceptibility and advancements in therapeutics and research; however, it has been largely unchanged over the last several decades. The most recent treatment recommendations consider the severity of infection, clinical presentation, and the polymicrobial nature of the disease. In addition, the role of novel organisms like Mycoplasma genitalium in PID is of emerging significance. PID treatment guidance offers oral and parenteral treatment options based on the patient's clinical status; however, deviations from the published guidelines are a general concern. Point of care (POC) testing for precision care, provision of adherence support, optimizing self-management and prevention strategies, and other alternative or synergistic approaches that maximize treatment outcomes will be instrumental for addressing the current challenges in PID diagnosis and management.