The tunability of nanocluster size, structure, and composition yields three approaches to optimizing their properties in discrete steps for a given task. The smallest step in size is a difference of a single atom, but more typically, specific numbers of atoms are geometrically and electronically stable, and thus it is difficult to isolate clusters resulting from the stepwise addition or exchange of single atoms. Similarly, for a given number of atoms, only one or a few structures are typically known. Tuning by doping 10 or by ligand exchange 11 can allow the fine-grained tuning of nanocluster properties, but can also make the purification of the resulting synthetic mixture much more challenging. Fine-tuning of molecules and coordination complexes is often achieved by chemical derivatization.As a result, well-developed frameworks exist for predicting how ligand derivatives affect electronic structure and properties of molecules and coordination complexes via bonding, 13 electron withdrawing and donating effects, 14 and steric effects, for example. Such a framework does not yet exist for nanoclusters, hampering the ability to rationally harness ligand chemistry to optimize nanocluster properties.