Providing novel treatments to help cancer patients live longer and have better lives remains one of the biggest challenges of the pharmaceutical industry. Today much is known about the molecular and genetic causes of cancers thus facilitating the development of novel targeted cancer drugs with improved risk-benefit ratios compared to contemporary broadly-acting, cytotoxic cancer drugs. Antisense therapy, e.g. the use of single stranded oligonucleotides as therapeutic modalities, provides the means to develop such targeted drugs, and in recent years this concept has enjoyed a major renaissance. Locked Nucleic Acid (LNA) is a novel, third generation RNA analogue that displays most if not all of the characteristics required to make potent and safe antisense drugs. Here we review the key properties of LNA oligonucleotides in the context of their use as safe and effective antisense drugs and provide a status on their therapeutic development in the field of cancer.