If malignant growth is considered the result of abnormal gene expression, it is reasonable to use antisense nucleic acids for the treatment of malignant diseases. Antisense oligonucleotides can specifically down-regulate gene expression, and a number of first-generation antisense compounds have entered human clinical trials. In this review, some aspects relevant for the development of antisense-based drugs, such as the selection of appropriate target sequences, cellular delivery, and design of a clinical study, are described, using bcr-abl-oncogene-directed antisense oligonucleotides as an example. In addition, potential target genes for antisense inhibition in hematology and oncology, including oncogenes and adhesion molecules, are summarized. Down-regulation of such adhesion molecules as members of the immunoglobulin superfamily and integrins may provide new modalities for mobilization of CD34+ hematopoietic stem cells into the peripheral blood. The review closes with an overview of ongoing clinical trials in the treatment of malignant diseases by antisense oligonucleotides.