Themodernbillion-dollardrug-discoveryprocessstronglyreliesonbothhi- throughput synthesis and screening methods. Whereas the latter is based on molecular biological methods, the ef?cient and reliable generation of c- pound collections often makes use of combinatorial chemistry. Discovered in the 1980s, this methodology was explored extensively in the 1990s by groups in academia and in industry. Without any doubt, combinatorial chemistry changed the whole drug-discovery process and found many applications in cropscience and the material sciences. However, since its implementation, solution- and solid-phase techniques have been competing with each other, and although many companies started theircombinatorialchemistryprogramwithsolid-phasetechniques,soluti- phase combinatorial methods have taken over and now account for appro- mately 25% of all combinatorial efforts. The syntheses of complex, non-polymeric structures, discovered in the 1960s by the late Bruce Merri?eld, was largely ignored in the context of solid supports, mainly due to the fact that appropriate synthesis techniques were not available. Since solid-phase chemical methodology strongly differs from traditional solution-phase chemistry, two chapters deal with this topic. The Brase group (Jung, Wiehn, Brase) gives an overview of multifunctional linkers, which can beusedforthegenerationofdiversity-orientedcollections,simplybycleavage fromresins. Still in its infancy, solid-phase reactions employ "simple" amide chemistry in most cases due to their high-yielding, reliable protocols. Ljungdahl, Br- ?eld, and Kann address solid-phase organometallic chemistry, which is now one ofthe great challenges in reliable solid-phase organicsynthesis.