The ability to manipulate gene expression by means of exogenously administered oligodeoxynucleotides complementary to specific sequences in the genome is clearly going to impact on many fields of biology and medicine including basic and clinical immunology. Also endogenously generated antisense RNA species are important in regulating gene expression. Antisense RNA has become a widely used tool for analysis of gene function and holds great promise for therapeutic use in the future. Thus, inhibition can take place on different levels (transcription, translation and aptamer binding). Avoiding unspecific reactions one has to use controls and well-designed oligonucleotides. Based on the studies described in this review, antisense oligonucleotides hold a great promise as a novel class of therapeutic agents in immunology as well as in oncology, neurology and viral infections.