The antisense was first imagined as the therapeutic drug at the end of 1970. After 20 years the antisense drugs have been hitting into the market from laboratory and clinical research. Antisense captures general attention with their promise of rational drug design and exquisite specification. But antisense drugs are far more difficult to produce than were originally anticipated. This article reviewed the current situation and present questions involved in their specificity, stability, potency, toxicology, intracellular delivery, administration routes and costs of manufacture, etc. It is likely that the antisense drugs will be a part of the pharmacopoeia in the future and benefit for treatment of human diseases with the solution of present questions.