Disease relapse remains the major cause of treatment failure in adults with acute myeloid leukaemia (AML). This reflects both the failure of current salvage regimens and the absence of effective strategies to secure long-term disease-free survival in those patients who achieve a second remission. Recent progress in understanding the pathogenesis of relapsed disease has enabled the identification of a variety of dysregulated molecular pathways and these now provide a rational basis for the design of novel targeted therapies. At the same time, advances in allogeneic stem-cell transplantation have permitted the extension of the curative potential of allografting to patients in whom it was previously contraindicated. As a result, a range of novel drug and transplant therapies has become available in patients with relapsed AML, and it is realistic to anticipate that a co-ordinated assessment of their clinical and biological impact will provide the basis for the design of future, more effective treatments in relapsed disease.