Breast cancer is a significant health problem in terms of both morbidity and mortality, with approximately 12% of women directly affected by this disease. Chemotherapy, given to patients with earlier stage disease, has a good survival impact and may contribute to cure. The failure of chemotherapeutic drugs to eradicate cancer cells in more advanced disease states may be due to intrinsic or acquired drug resistance, including multiple drug resistance. The drug resistance observed in breast cancer patients is likely to be multifactorial, involving mechanisms such as altered expression and/or activity of drug efflux pumps, nuclear DNA-binding enzymes, metabolizing and conjugating enzymes, and mismatch repair deficiency. More extensive transcriptomic and proteomic analyses of breast tumour and normal biopsies, followed by functional genomic studies in relevant cell line models, should increase our understanding of this phenomenon and lead to therapies being individualized for identifiable subgroups of breast cancer patients.