Chemoresistance to platinum-based chemotherapy for ovarian cancer in the advanced stage remains a formidable concern clinically. Increasing evidence has revealed that apoptosis represents the terminal events of the anti-tumor mechanisms of a number of chemical drugs and has a close association with chemoresistance in ovarian cancer. The B-cell lymphoma-2 (Bcl-2) family plays a crucial role in apoptosis and has a close association with chemoresistance in ovarian cancer. Some drugs that target Bcl-2 family members have shown efficacy in overcoming the chemoresistance of ovarian cancer. A BH3 profiling assay was found to be able to predict how primed a cell is when treated with antitumor drugs. The present review summarizes the role of the Bcl-2 family in mediating cell death in response to antitumor drugs and novel drugs that target Bcl-2 family members. The application of the new functional assay, BH3 profiling, is also discussed herein. Furthermore, the present review presents the hypothesis that targeting Bcl-2 family members may prove to be helpful for the individualized therapy of ovarian cancer in clinical practice and in laboratory research.