Naturally occurring cyclic peptides offer great potential as leads for drug design. This talk will focus on a class of cyclic peptides known as cyclotides, which are topologically unique in that they have a head-to-tail cyclised peptide backbone and a cystine knotted arrangement of disulfide bonds. This makes them exceptionally stable to chemical, thermal or enzymatic treatments and, indeed, they are amongst nature’s most stable proteins. Because of their exceptional stability and well-defined structures cyclotides make excellent templates for drug design applications. This presentation will describe the discovery of cyclotides in plants, their structural characterization, and applications in drug design for the treatment of cancer, obesity, autoimmune disease (multiple sclerosis) and pain, as well as our efforts towards the expression of pharmaceutical cyclotides and other cyclic peptides in plant ‘biofactories’, particularly in Arabidopsis, tobacco and petunia.