Chemotherapy has a proven role in advanced and metastatic gastric cancer (AMGC) significantly improving quality of life and prolonging survival compared with best supportive care alone. Multiple regimens have been explored. The choice of treatment should be individualized and tailored to the patient's overall conditions and preference. This manuscript is divided into two sections. The first section illustrates the results of a phase II trial combining weekly irinotecan and low dose capecitabine in the management of untreated AMGC patients. The second section aims to identify the current optimal place of this combination in the management of AMGC in the light of the latest advances. In this manuscript we detail our phase II trial which showed objective response rate of 47% (15 patients), disease stabilization of 28% (9 patients), and overall tumor control rate of 75% (24 patients). Median time to progression and overall survival were 5.8 and 8 months, respectively. Grades III-IV toxicities were reported in 7 cases. Low-dose capecitabine plus irinotecan is effective in the treatment of AMGC with an acceptable toxicity profile. Compared to the recent published data, this combination is indicated in the second-line treatment of AMGC and in the first-line treatment where a contraindication for docetaxel- and/or oxaliplatin-based regimen is present.