Oligometastasis represents an intermediate disease stage between localized and widely metastatic cancer. Efficient identification of patients with oligometastasis remains a barrier for accrual on clinical trials of oligometastasis-directed therapy. Here we review the prospect of circulating tumor DNA-based monitoring to promote sensitive, specific, and cost-efficient detection of cancer recurrence during posttreatment surveillance. Thus, an impetus for the development and implementation of clinical-grade circulating tumor DNA assays should be for the positive impact they will have on clinical investigations of oligometastasis-directed therapy.