The article discusses the potential of targeting G-quadruplexes in gene promoters as a novel anticancer strategy. G-quadruplexes are four-stranded DNA structures that are over-represented in gene promoter regions and can be stabilized by small molecules. The authors highlight the therapeutic potential of targeting these structures, particularly in genes such as *MYC*, *KIT*, and *KRAS*, which are frequently overexpressed in various cancers. They review the evidence for the existence of G-quadruplexes in gene promoters, the structural characteristics of these structures, and the identification of proteins that modulate their formation and function. The article also discusses the development of small-molecule ligands that can stabilize or disrupt G-quadruplexes, including the first-in-class compound quarfloxin, which showed promise in Phase II clinical trials. Despite the challenges in drug development, the authors suggest that the diversity of G-quadruplex structures could enhance selectivity, making them a promising therapeutic target.The article discusses the potential of targeting G-quadruplexes in gene promoters as a novel anticancer strategy. G-quadruplexes are four-stranded DNA structures that are over-represented in gene promoter regions and can be stabilized by small molecules. The authors highlight the therapeutic potential of targeting these structures, particularly in genes such as *MYC*, *KIT*, and *KRAS*, which are frequently overexpressed in various cancers. They review the evidence for the existence of G-quadruplexes in gene promoters, the structural characteristics of these structures, and the identification of proteins that modulate their formation and function. The article also discusses the development of small-molecule ligands that can stabilize or disrupt G-quadruplexes, including the first-in-class compound quarfloxin, which showed promise in Phase II clinical trials. Despite the challenges in drug development, the authors suggest that the diversity of G-quadruplex structures could enhance selectivity, making them a promising therapeutic target.