Adjuvant systemic therapy of breast cancer is now a well-established treatment resulting in improved survival. However, the available evidence suggests that it is most unlikely that an individual woman will be cured as a consequence of such treatment. There is, therefore, a pressing need for more effective therapy, particularly for younger women whose degree of axillary nodal involvement indicates a high risk of subsequent relapse. The case for using myelo-ablative chemotherapy for such women is presented in this article. In a subsequent publication we will discuss the clinical data to suggest that such an approach is not only possible with acceptable toxicity, but also could actually offer the increased cure rate sought by clinicians and patients alike.