Cyclotides are small disulphide-rich peptides found in plants from the violet (Violaceae), coffee (Rubiaceae) and cucurbit (Cucurbitaceae) families. They have the distinguishing structural features of a macrocyclic peptide backbone and a cystine knot made up of six conserved cysteine residues, which makes cyclotides exceptionally stable. Individual plants express a suite of cyclotides in a wide range of tissue types, including leaves, flowers, stems and roots and it is thought that their natural function in plants is as defence agents. This proposal is supported by their high expression levels in plants and their toxic and growth retardant activity in feeding trials against Helicoverpa spp. insect pests. This review describes the structures and activities of cyclotides with specific reference to their insecticidal activity and compares them with structurally similar cystine knot proteins from peas (Pisum sativum) and an amaranthus crop plant (Amaranthus hypocondriancus). More broadly, cystine knot proteins are common in a wide range of organisms from fungi to mammals, and it appears that this interesting structural motif has evolved independently in different organisms as a stable protein framework that has a variety of biological functions.