Recombinant antibodies have found numerous important applications as therapeutics and diagnostic reagents. However, they can be tedious and expensive to generate in very large quantities. In this issue, Kodadek and colleagues have studied the potential to generate peptide-binding peptides as alternative reagents to antibodies for diagnostic purposes (see p. 71). They first developed a genetic screen that allowed them to isolate peptides that could recognize their targets with high specificity. They then showed that the strengths of the peptide–peptide interactions, although much weaker than most antibody-antigen interactions, were sufficient to support immunoblot and affinity purification applications.