Primary debulking surgery followed by platinum-based chemotherapy remains the standard treatment of patients with stage III-IV epithelial ovarian cancer. Neoadjuvant chemotherapy is an alternative treatment regimen that can be considered in selected patients. Complete cytoreduction, both through primary debulking surgery and interval debulking surgery, has a major positive effect on survival and should be the goal, even if this requires extensive surgery. When thorough assessment of tumor spread and performance status of the patient indicates that complete primary cytoreduction is not feasible without unacceptable morbidity, then alternative therapeutic strategies, such as neoadjuvant chemotherapy, must be considered. Such patients can be offered the option of interval debulking surgery after checking their response to neoadjuvant chemotherapy and resolution of the initial obstacles for primary debulking surgery (i.e. complete response of irresectable disease and improvement of the performance status). Current evidence suggests that a selected group of patients with International Federation of Gynecology and Obstetrics stage III-IV ovarian cancer will benefit from NAC-IDS. Research is ongoing to identify patients who might derive the greatest benefit from neoadjuvant chemotherapy followed by interval debulking surgery, instead of primary debulking surgery, on the basis of radiological, genetic, pathological, and immunological variables. In this review, we discuss current knowledge about the clinical significance of primary debulking surgery and neoadjuvant chemotherapy in advanced ovarian cancer and discuss unanswered questions in the field.