In recent years, it has been shown that the central dogma of molecular biology with an underlying "one gene-one protein" concept is no longer viable. Instead, the transcriptome is dominated by non-coding RNA transcripts. Several classes of non-coding RNAs, including ribosomal RNAs, transport RNAs, microRNAs, small nuclear RNAs and a few others have been relatively well characterized. At the same time, there is one family in the non-coding transcriptome, long non-coding RNAs (lncRNAs), which, despite being the most abundant, remains structurally and functionally mysterious. Initially considered to be transcriptional noise, lncRNAs have now come under intense scrutiny, and the number of papers on lncRNAs has grown exponentially. Due to their ability to interact with virtually all classes of biomolecules, lncRNAs appear to have unique and enormous functional potential. Such a broad action of lncRNAs promises potential therapeutic implications. It is challenging to target lncRNAs by traditional medicines, such as small molecules and antibodies, but oligonucleotide-based therapies, which have been considerably improved within the last two decades, may be a perfect match. Despite translational studies of lncRNAs being in their infancy, these approaches already appear to be of therapeutic value. Here we discuss basic biology and functions of lncRNAs as well as lncRNA-dependent mechanisms of pathogenesis. We also discuss oligonucleotide-based drugs as a tool to harness those mechanisms for therapeutic purposes.