Eighteen years ago, antisense oligonucleotide therapeutics that can selectively knock out disease-causing genes could easily have been viewed as science fiction, Yet today, through much persistence and focused investment, the technology has nearly evolved to the point of realization, A number of first-generation antisense compounds have entered human clinical trials, Some of these compounds appear to work by an antisense mechanism to inhibit the expression of disease-causing genes, while others probably work by unanticipated, yet clinically beneficial, mechanisms, In this review, the current status of antisense oligonucleotide development will be described as it relates to two areas of concentrated effort: antiviral and anticancer applications.