Patients with recurrent low-grade serous ovarian cancer (LGSOC) have multiple options for treatment: chemotherapy with/without bevacizumab, bevacizumab, or endocrine therapy. While all of these are viable and appropriate options, MEK inhibitors are a key treatment option that should be considered at time of first recurrence in all patients with LGSOC. Trametinib is now NCCN compendium listed for recurrent LGSOC. While MEK inhibitors have shown clear efficacy in the treatment of recurrent LGSOC, they can cause considerable toxicity, with rash, diarrhea, edema, and ocular toxicity all commonly observed. These toxicities can lead to dose interruptions and dose reductions, causing decreased dose intensity that translates into a missed opportunity for optimal response. MEK inhibitors are therefore best administered early in the disease course, at time of first relapse, when patients generally have the best performance status and are most likely to be able to tolerate continuous therapy without dose reduction.