Introduction: Apatinib is an orally administered small-molecule vascular endothelial growth factor receptor 2 inhibitor. It has been approved and indicated for advanced gastric cancer after the failure of two or more lines of systemic therapy in China. Areas covered: This review summarizes the mechanisms, clinical applications and safety evaluations of apatinib. Apatinib is well tolerated, and its most common adverse effects include hand-foot syndrome, hypertension, proteinuria and neutropenia. Its major grade 3/4 adverse effect is hand-foot syndrome. Expert opinion: Apatinib is an effective and safe drug for advanced gastric cancer patients that shows tolerable and manageable toxicity. However, it should be avoided in patients with a bleeding tendency or at risk of perforation. Worldwide assessments of its efficacy and safety are needed. Additionally, the early presence of antiangiogenesis-related adverse events may predict the drug efficacy of apatinib. List of Abbreviations: GC: gastric cancer; mOS: median overall survival; TKI: tyrosine kinase inhibitor; EGFR: epidermal growth factor receptor; HER2: human epidermal growth factor receptor 2; VEGFR: vascular endothelial growth factor receptor; mTOR: mammalian target of rapamycin; HGFR: hepatocyte growth factor receptor; HR: hazard ratio; CI: confidence interval; mPFS: median progression-free survival; T-max: median time to peak drug concentration; C-max: maximum plasma drug concentration; AUC(0-24h): areas under the concentration-time curve 0-24 h; CFDA: China Food and Drug Administration; FAS: full analysis set; ORR: objective response rate; DCR: disease control rate; PR: partial response; SD: stable disease; MTD: maximum tolerated dose; AEs: adverse events; IC50: 50% median inhibitory concentration