Twenty years of published literature was reviewed for chemotherapy regimens used to treat patients with acute myeloid leukemia (AML) in first relapse. Thirty-one trials containing at least 20 patients in first relapse and information on patient age, duration of first complete remission (CR1), and rate of second complete remission (CR2) were analyzed. These trials included 10 retrospective studies with CR2 rates ranging from 30 to 64%, two phase II single-agent studies with CR2 rates of 8 and 25%, 15 phase II combination-agent studies with CR2 rates ranging from 14 to 87%, and four phase III randomized studies with CR2 rates ranging from 40 to 89%. When reported, median duration of CR2 was < or = 14 months and overall median survival was < or = 12 months. The probability of 3-year survival ranged from 8 to 29%. Combination therapies resulted in higher CR2 rates but were associated with longer duration of myelosuppression and greater incidence of mucositis. None of the reviewed regimens provided durable remissions for the majority of AML patients in first relapse. The CR2 rates were closely associated with age and duration of CR1. Therefore, considering the poor clinical outcomes of patients with AML in first relapse, improved therapies need to be developed.