Emerging research suggests that long noncoding RNAs (ncRNAs) may play a role in the basic fabric of gene regulation in human cells. Mechanistic studies carried out on a small subset of antisense ncRNAs have begun to link RNA-mediated modifications of DNA and chromatin structure with gene expression, implicating ncRNAs in the regulation of transcription. Meanwhile, genome-wide studies have revealed that transcription of ncRNAs is far more ubiquitous than previously thought and suggest a more pervasive role for ncRNAs. This review will describe the current state of research regarding gene regulation by ncRNAs and highlight major techniques used in the field. Furthermore, the potential for therapeutic applications based on ncRNA regulation will also be discussed.