The choice of therapy for first relapse of low-grade serous carcinoma – the focus of this debate – is based on several key factors, including type of primary therapy, efficacy and side effects of standard regimens, availability of clinical trials, and patient preferences. Three clinical trials have provided evidence that MEK inhibitors possess promising activity against recurrent disease. However, they are associated with potentially significant side effects. There are several options for treatment of relapse, including chemotherapy, endocrine therapies, bevacizumab, and targeted agents. However, there is no standard for sequencing of these drugs. My preference is for a clinical trial at first relapse. Off protocol, for women who have not previously received an aromatase inhibitor, this is my recommendation for first relapse. For those who have previously received an aromatase inhibitor, based on the findings in the MILO trial and the therapeutic index of MEK inhibitors, pegylated liposomal doxorubicin is my preference at first relapse.