Thiarabine is undergoing clinical trials. In support of that effort combination therapy of thiarabine plus six clinical anticancer agents was evaluated using various human tumor xenograft models. The antitumor activity of thiarabine in combination appeared to be greater than additive with irinotecan (DLD-1 colon), paclitaxel (PC-3 prostate), cisplatin (PC-3 prostate), or cyclophosphamide (RL lymphoma), additive with irinotecan (NCI-H460 NSCLC), cisplatin (NCI-H460 NSCLC) or methotrexate (CCRF-CEM leukemia), and less than additive with irinotecan (HT29 colon), paclitaxel (NCI-H460 NSCLC) or cisplatin (NCI-H23 NSCLC). Combining thiarabine with irinotecan, paclitaxel, cisplatin, or cyclophosphamide should receive consideration in the clinical treatment of cancer. © 2012 Copyright Taylor and Francis Group, LLC.