Doxorubicin is an anthracycline chemotherapeutic agent commonly used in the treatment of breast and other cancers, however major cardiotoxicities limit its usage. ABT-737, a small molecule inhibitor of bcl-2, bcl-xL and bcl-w, has been used in combination with doxorubicin to increase apoptosis and tumour cell sensitivity to doxorubicin. While demonstrated effective in other cancer types, investigation into the pathways of enhanced cell death is limited, and effects are unknown in breast cancers. This study aimed to investigate the effects of ABT-737 in combination with doxorubicin on T47D breast cancer cells and gain further understanding into the molecular pathways involved. A series of assays were carried out to investigate the effects of ABT-737 in combination with doxorubicin on T47D cell death, cell cycle arrest, caspase activation and apoptosis. The combination resulted in a synergistic increase in cell death compared to individual treatments. There was a significant increase in condensed chromatin in cells treated with the combination when compared to individually treated cells though this was not associated with an increase in caspase activation which was only observed in individual treatments, not in combination treatment. Doxorubicin and ABT-737 treatment alone resulted in cell cycle arrest in S or G2/M phase, which has been described previously, but the combination caused cell cycle arrest in G1 phase. A human apoptosis array, revealed a decrease in the levels of cytochrome c, XIAP, HSP70 and HTRA2. Treatment with doxorubicin alone resulted in a caspase dependent form of cell death. However, when combined with ABT-737 this apoptotic pathway was actually inhibited, suggesting that cell death was occurring through caspase-independent mechanisms. Cell cycle arrest, and therefore initiation of DNA repair, was also altered. Doxorubicin alone caused cell cycle arrest in S and G2/M, suggesting HR involvement, while the combination caused accumulation in G1, therefore more NHEJ involvement. Although the synergism was therapeutically beneficial further elucidation of the pathways involved is required.