Due to their small size and specific binding properties, peptides are very suited to interfere with protein-protein interactions and thus are ideal drug candidates aiming at such targets in the complex cellular interactome. Peptides can easily be selected from natural or artificial peptide libraries for any target and further optimized by in silico analysis, chemical synthesis, and the introduction of non-natural amino acids. Here we review the current status of peptide drugs with special emphasis on the inhibition of HIV-1.