Drug discovery is costly and time-consuming, but it will become easier and simpler if a drug could be developed from an old one with well-documented investigations associated with pharmacology, pharmacokinetics, toxicology and clinical safety. In terms of hematological malignancies, several successful drugs have been discovered and developed from old ones such as arsenic trioxide for acute promyelocytic leukemia and thalidomide for multiple myeloma. In this review, we discussed the latest advancement in exploring old drugs for the treatment of hematological malignancies.