Gastric cancer is one of the major causes of cancer-related deaths. Many patients with metastatic gastric cancer after first-line chemotherapy received salvage chemotherapy in routine clinical practice. Recent phase Ⅲ trials demonstrated substantial prolongation of overall survival to support this chemotherapy or targeted therapy as a second-line treatment. Both ramucirumab monotherapy and ramucirumab plus paclitaxel were approved by FDA in patients with previously treated advanced gastric or gastroesophageal junction adenocarcinoma. In addition, paclitaxel, irinotecan, or docetaxel monotherapy is also recommended for preferred regimens. This review will summarize chemotherapy or targeted therapy as a second-line treatment in advanced gastric cancer.