Since its first regulatory approval more than 10 years ago, oncologists have gained wide experience in using the oral fluoropyrimidine, capecitabine, as monotherapy or in combination with other agents and the body of evidence supporting these approaches continues to grow. Alongside this increasing experience has been the appearance of new challenges in patient management. We now recognise several different biological subtypes of breast cancer, such as HER2-positive disease. The standard of care in these tumours comprises anti-HER2 therapy, and phase III data show that capecitabine can be effectively combined with such agents. Another increasingly prominent and currently unresolved issue resulting from more effective treatment of metastatic disease is the management of patients with brain metastases. The introduction of new, well-tolerated, oral chemotherapies also provides the opportunity for longer duration of therapy. These new clinical scenarios are discussed in the current review.