The importance of salen ligands in homogeneous catalysis and material chemistry has unambiguously been demonstrated over the last two decades. In the majority of the existing studies, C2-symmetrical salen complexes have been used as catalysts for many organic conversions; however, the amount of structures that can become available for catalyst fine-tuning by changing the peripheral groups on the bridging unit and the aryl side groups is limited. In order to widen their scope in catalytic procedures new designs of salen structures have been probed, and above all unsymmetrical versions. In this respect, it has become increasingly important to develop reliable and efficient preparative methods for these nonsymmetrical salen compounds, and more particularly ligands with two differently substituted salicylideneimine groups. The presence of a single functional group suitable for connection to various supports has great advantages, since full access of the catalytic sites in the supported structure may be preserved and new and/or improved catalytic properties can be tailored. On the other hand, different functions on both sides of the central N2O2 unit can be used to force the formation of specific (supramolecular) architectures. This review discloses the general methods available for the preparation of unsymmetrical salen ligands/complexes and the most important fields of their application.