G‐quadruplexes are secondary structures formed in G‐rich sequences in DNA and RNA. Considerable research over the past three decades has led to in‐depth insight into these unusual structures in DNA. Since the more recent exploration into RNA G‐quadruplexes, such structures have demonstrated their in cellulo existence, function and roles in pathology. In comparison to Watson‐Crick‐based secondary structures, most G‐quadruplexes display highly redundant structural characteristics. However, numerous reports of G‐quadruplex motifs/structures with unique features (e.g. bulges, long loops, vacancy) have recently surfaced, expanding the repertoire of G‐quadruplex scaffolds. This review addresses G‐quadruplex formation and structure, including recent reports of non‐canonical G‐quadruplex structures. Improved methods of detection will likely further expand this collection of novel structures and ultimately change the face of quadruplex‐RNA targeting as a therapeutic strategy.