Adjuvant use of anthracycline-taxane combination therapy is an accepted strategy in the management of high-risk early-stage breast cancer. However, the introduction of this regimen raises the question of how best to manage those patients who relapse following adjuvant therapy, and whether there is a role for rechallenging in the metastatic setting with the same agent, or class of agent, that has been utilized in the adjuvant setting. This Review examines the evidence for rechallenging with both anthracyclines and taxanes, and highlights the issues that need to be examined in the context of future clinical trials.