Background: Gastric cancer (GC) is characterized by aggressive behavior and a high mortality rate. The diagnosis of GC is challenging because the GC is often diagnosed in an advanced stage. The use of tumor markers is a putative way to improve the detection and treatment in patients with GC. Summary: In this article, we review the significance of serum carbohydrate antigen (CA) 19-9, carcinoembryonic antigen (CEA), and CA 72-4 in GC. The results from different studies regarding the diagnostic and prognostic role of CA 19-9, CEA, and CA 72-4 in GC are encouraging, but inadequate sensitivity and specificity obstruct their use as standardized and unconditionally reliable markers in GC. New prospective clinical trials are mandatory for clarifying their value in GC. Key Message: CA 19-9, CEA, and CA 72-4 should not be used for screening and early diagnosis in GC, whereas they are beneficial in the detection of late GC. CA 19-9, CEA, and CA 72-4 could be used as prognostic and monitoring tools in GC, and their combined measurement in shorter periods of time is the best method to increase sensitivity and specificity. Practical Implications: Serum CA 19-9, CEA, and CA 72-4 are useful diagnostic and prognostic tumor markers in GC.