Serum cancer antigen 125 (CA125) is widely used in ovarian cancer to monitor the effectiveness of therapy both in first line and recurrence. It is also widely used during follow-up, where it is able to identify a percentage of patients with asymptomatic recurrence. Although a recent Medical Research Council (UK)/European Organisation for Research and Treatment of Cancer trial has demonstrated that early chemotherapy in asymptomatic patients based only on CA125 increase does not prolong survival, we still believe that CA125 monitoring should be prescribed to patients during follow-up. In fact, it can help to identify patients who should undergo radiology in order to select those that can benefit from surgery or from early treatment before the onset of symptoms, which are usually related to an excessive disease burden. The delay of disease symptoms, such as those associated with the appearance of ascites or bowel occlusion, is in our view an important goal of our treatment of recurrence. Moreover, research should be done in patients with asymptomatic CA125 increase in order to identify more effective therapies that will improve survival. Finally, the reliability of CA125 as a surrogate of response under treatment with biological agents should be validated in prospective trials.