We discuss the role of the metal-ligand (M-L) interfaces in the chemistry of ligand protected, atomically precise noble metal clusters, a new and expanding family of nanosystems, in solution as well as in gas phase. A few possible mechanisms in which the structure and dynamics of M-L interfaces could trigger intercluster exchange reactions are presented first. How interparticle chemistry can be a potential mechanism of Ostwald ripening, a well-known particle coarsening process, is also discussed. Reaction of Ag59(2,5-DCBT)32 (DCBT = dichlorobenzenethiol) with 2,4-DCBT leading to the formation of Ag44(2,4-DCBT)30 is presented, demonstrating the influence of the ligand structure in ligand-induced chemical transformations of clusters. We also discuss structural isomerism of clusters such as Ag44(SR)30 (-SR = alkyl/aryl thiolate) in gas phase wherein the occurrence of isomerism is attributed to the structural rearrangements in the M-L bonding network. Interfacial bonding between Au25(SR)18 clusters leading to the formation of cluster dimers and trimers is also discussed. Finally, we show that desorption of phosphine and hydride ligands on a silver cluster, [Ag18(TPP)10H16]2+ (TPP = triphenylphosphine) in gas phase, lead to the formation of a naked silver cluster of precise nuclearity, such as Ag17+. We demonstrate that the nature of the M-L interfaces, i.e., the oxidation state of metal atoms, structure of the ligand, M-L bonding network, etc., play key roles in the chemical reactivity of clusters. The structure, dynamics and chemical reactivity of nanosystems in general are to be explored together to obtain new insights into their emerging science.