Despite significant advances that have been made in recent years, there is still an urgent need for novel, more effective and less toxic therapeutics for human cancer. Among many new molecular therapeutics being explored for cancer therapy, antisense oligonucleotides are a promising nucleic acid-based approach, with numerous antisense agents being evaluated in preclinical studies and several anticancer antisense drugs in clinical trials. Although there are still a few problems facing the development of antisense strategies for cancer therapy, with progress made in chemical modifications, target selection and drug delivery systems, antisense oligonucleotides are emerging as a novel approach to cancer therapy used alone or in combination with conventional treatments such as chemotherapy and radiation therapy.