Gastric carcinoma remains a global healthcare challenge representing a fifth of all new cancer diagnoses worldwide. Despite improvements in oncological and surgical treatment, prognosis remains poor, particularly in patients who present with advanced disease. Novel therapeutic strategies have begun to emerge however, including trastuzumab and the checkpoint inhibitors nivolumab and pembrolizumab that have demonstrated consistent efficacy in patients with HER2-positive or PD-L1-positive tumours respectively. However, these are not effective in all patients and alternative therapeutic strategies need to be urgently sought. In this chapter, we discuss the role of anti-apoptotic proteins in resistance to chemotherapy in solid tumours, specifically gastric cancer, and explore the evidence that Bcl-2 Homology 3 (BH3) mimetics may have a role in the treatment of gastric carcinoma. We discuss how the genetic aberrations commonly observed in solid cancers such as gene amplifications may potentially make gastric carcinoma more amenable to these inhibitors. Finally, we examine how the BH3 mimetics have been combined with other drugs, highlighting the potential that synergistic combinations may further improve outcomes. Understanding how cells are resistant to apoptosis could help in the design of future targeted therapies.