Among all conditions that could affect female patients during their life experiences, genital tract infections, endometriosis, pelvic pain, vulva and vagina disorders are considered common gynecological problems. Some of these pelvic disorders can present a major challenge to health care providers due to their complex aetiology and poor response to therapy and therefore, quite often, are difficult to manage. An example is the case of bacterial infections, considering that around 50–60% of women will experience some urinary tract infections (UTIs) in their lifetime. A growing evidence of literature documents the association between pelvic pain disorders and other painful conditions as bladder symptoms (postcoital cystitis, urethralgia/urethrodynia, painful bladder syndrome), irritable bowel syndrome, fibromyalgia, and headache, up to sexual comorbidities as vulvar pain or painful intercourse, with its cohort of secondary loss of desire, vaginal dryness, orgasmic difficultiesand sexual dissatisfaction. It is clear that pelvic pain and its comorbidities can have negative consequences for women’s quality of life and can deeply impact their ability to have children and in some cases, if neglected, can even threaten the life of the patient. Immediate and appropriate diagnosis, cure and adequate care would prevent each disease or disorder becoming chronic and, even worse, incurable. This is the case of interstitial cystitis/bladder pain syndrome and vulvodynia, which are considered among the main causes of chronic pelvic pain in women. Management requires knowledge of all pelvic organ systems and their association with other systems and conditions, including musculoskeletal, neurologic, urologic, gynaecologic and psychological aspects. However, some patients are considered resistant to standard therapy if their condition failed to respond to classic therapies. Physicians are required to deeply investigate on the causes of pelvic pain and to realise that no single treatment is successful in all women, therefore a multi¬dis¬cip¬linary and multimodal treatment is considered to be the new state of the art. Novel treatment strategies has also to be considered to offer a practical therapeutic alternative in case of failure of classic treatment options.