Disulfide-rich peptides typically exhibit high potency and selectivity for their molecular targets and therefore represent promising drug leads. The disulfide bonds within these peptides help to define the three-dimensional shape of the peptide, which is often crucial for function, and also provide stability against denaturation and proteases. However, the presence of multiple disulfide bonds in a peptide can often make the synthesis challenging as multiple disulfide regioisomers can be formed. In this talk I will present our work on elucidating the structure/function activity of disulfide-rich peptides, the challenges we have faced in correctly folding these peptides and how these studies have allowed us to minimize some peptides to key bioactive epitopes that are much simpler and efficient to produce synthetically.