In this issue, Park and Raines (see p. 847) describe the development of a genetic selection method for searching peptide libraries for molecules that inhibit protein–protein interactions. They demonstrate their method using the dimerization of HIV-1 protease as a target. An inactive version of dimeric HIV protease is tethered to the bacteriophage lambda repressor DNA-binding domain. Because the DNA-binding domain functions as a dimer, dimerization of which is mediated by the HIV protease domain, this system can be used to study peptides that disrupt protein–protein interactions in HIV protease. The authors used the approach to screen a library of peptides for those able to interfere with the dimerization process by coupling the lambda operator to selectable markers. The method allowed them to find rare peptides that interfere with protein interactions.