Circulating tumor cells (CTC) have been focused on as a target for detecting occult tumors, predicting therapeutic responses and prognoses, and monitoring postoperative recurrence in the clinical management of patients with various malignancies, including gastric cancer. Recent advances in molecular diagnostic tools have contributed to high sensitivity and specificity for the detection of CTC. A conspicuous disparity exists in the incidence of CTC among studies. However, a close relationship has been reported between positivity for CTC and well-known prognostic clinicopathological factors including depth of tumor invasion, lymph node metastasis, stage, and lymphatic and venous invasion in patients with gastric cancer. According to most studies published on the clinical impact of CTC, the presence of CTC negatively affects the prognosis of patients with gastric cancer. Moreover, the study of CTC based on a meta-analysis demonstrated their importance as a poor prognostic indicator. In clinical management, pre- and post-therapeutic monitoring of CTC using liquid biopsy may be useful for early detection of subclinical patients or disease recurrence, prediction of tumor progression, and administrative control of adjuvant chemotherapy. Although their functional properties remain unclear, molecular profiling of CTC may contribute to the development of personalized treatment that effectively inhibits tumor progression in patients with advanced gastric cancer. We herein review the clinical significance of CTC as a promising blood marker and therapeutic target in patients with gastric cancer.