The conventional view of gene regulation in biology has centered around protein-coding genes via the central dogma of DNA-->mRNA-->protein. The discovery of thousands of long non-coding RNAs (lncRNAs) has certainly changed our view of the complexity of mammalian genomes and transcriptomes, as well as many other aspects of biology including transcriptional and posttranscriptional regulation of gene expression. Accumulating reports of misregulated lncRNA expression across numerous cancer types suggest that aberrant lncRNA expression may be a major contributor to tumorigenesis. Here, we summarize recent data about the biological characteristics of lncRNAs in cancer pathways. These include examples with a wide range of molecular mechanisms involved in gene regulation. We also consider the medical implications, and discuss how lncRNAs can be used for cancer diagnosis and prognosis, and serve as potential therapeutic targets. As more examples of regulation by lncRNA are uncovered, one might predict that the large transcripts will eventually rival small RNAs and proteins in their versatility as regulators of genetic information.