Over the last decade or so there has been an escalation in the demand for synthetic peptides for a variety of purposes. Since solid-phase peptide synthesis (SPPS) lends itself easily to automation, the first steps taken were to design and produce machines with increased numbers of reaction vessels, so that different peptides could be synthesized in parallel. A way around the problem is to synthesize peptide mixtures (known as peptide libraries) in a controlled manner, rather than attempting to synthesize each peptide separately. The origins of peptide library synthesis can be traced back to Geysen who, in an effort to develop a more efficient method for epitope mapping, designed an apparatus for the parallel synthesis of 96 peptides. When larger libraries are to be synthesized by the split-and-combine method, care must be taken to use a sufficiently large initial amount of resin.