In addition to the familiar duplex DNA, certain DNA sequences can fold into secondary structures that are four-stranded; because they are made up of guanine (G) bases, such structures are called G-quadruplexes. Considerable circumstantial evidence suggests that these structures can exist in vivo in specific regions of the genome including the telomeric ends of chromosomes and oncogene regulatory regions. Recent studies have demonstrated that small molecules can facilitate the formation of, and stabilize, G-quadruplexes. The possible role of G-quadruplex-interactive compounds as pharmacologically important molecules is explored in this article.