Image-guided core biopsy of the omentum and peritoneum was described a decade ago and has since been validated in a number of large studies as a safe and effective means of providing a tissue diagnosis in patients with undiagnosed peritoneal disease. Some studies have addressed its ability for determining whether peritoneal infiltration and/or omental masses in patients with prior malignancy represent recurrent disease or a new disease process. Others have focused on the specific issue of women suspected to have advanced peritoneal carcinomatosis from ovarian or primary peritoneal cancer where the primary management of the patient is directed by the tissue diagnosis. The initial management of many of these women, especially those with advanced disease or substantial comorbidity, is with primary chemotherapy. With current clinical trials for ovarian cancer directed to specific morphological subtypes of the disease, image-guided core biopsy offers a rapid and well tolerated nonsurgical means of providing this information. In this Review, we discuss the technique and its clinical applications, and critically examine the currently available alternative options.