Relapse is the most prevalent cause of treatment failure and death in patients with acute myeloid leukaemia. Because only a minority of patients who experience relapse will derive durable benefit from current reinduction and salvage therapy, prognostic factors and predictive models have been developed. Achievement of a second complete remission and the application of salvage allogeneic stem cell transplantation represent crucial objectives for reaching long-term disease-free survival and improving the prognosis of patients with acute myeloid leukaemia in first relapse. Combination chemotherapy schedules that include high-dose cytarabine are frequently used in therapeutic efforts of attaining a second complete remission. In relapsed acute myeloid leukaemia with poor risk genetic features or those with early relapse after previous exposure to high-dose cytarabine, investigational drugs may be the preferred choice. The search for improved treatment with novel agents in clinical trials represents an active area of research.