The preparative and materials chemistry of high nuclearity metal-chalcogen (S, Se, Te; “E”) nanocluster complexes has evolved with the advent of new reaction strategies and the design of new reagents although the assembly of polynuclear complexes of the heavier congeners Se and Te is still often limited by the inherent instability or difficulty in handling of the chalcogen precursors.Polynuclear metal-chalcogenolates (M−ER) and -chalcogenides (M−E) of these heavier congeners possess rich photophysical properties and their structures are often unique due to the bonding modes displayed by the highly polarizable chalcogen centres. Metal-chalcogen nanoclusters can be defined as nanometer sized, polynuclear complexes which can contain tens to hundreds of metal/chalcogen core atoms that can be prepared and isolated as single crystals and thus for which complete structural information can be obtained via single crystal X-ray analysis. The controlled assembly of these materials is a major focus of our research programs. They differ from nanoparticles which are often larger and possess a certain (ideally, small) size dispersity such that characterization is achieved using other analytical methods (electron microscopy, powder X-ray diffraction, light scattering). The study of the photophysical properties of structurally-characterized semiconductor nanoclusters is important because the effects of polydispersity are removed versus nanoparticles. With size homogeneity and long range ordering in the crystal, they allow for investigations of quantum confinement effects at the lower size limit of “quantum dots” and of collective properties in the crystal. The chemistry of these molecular materials is being developed for photovoltaic and sensing applications.