In alloy castings fine and equiaxed grains are desirable, resulting in improved mechanical properties, an improved castability, reduction of defects and less likelihood of hot tearing. The final grain size of an alloy casting arises from the interaction of the casting process, the solute content and the number of inoculating particles. Grain refinement by inoculation has been extensively investigated for several decades, mainly on the field of aluminium alloys both, helping to understand the mechanism of grain refinement and to develop efficient master alloys. In contrast, copper alloys are less investigated. Despite the numerous work that has been performed within the last decades, admittedly creating outstanding results, they were found to be rather of empirical nature and reveal that grain refinement of copper based alloys seems to be strongly dependent on the alloy system, the solute contents, trace elements and impurities and furthermore on the casting conditions. Due to different alloy systems under investigation, the addition of several alloying elements and varying casting conditions, there is still a lack of detailed fundamental knowledge of the grain refinement mechanism. The intention of this work is to contribute substantially to the understanding of grain refinement of copper alloys by elucidation of growth restriction mechanism, potential nucleation sites and to contribute to the understanding of inclusion control from thermodynamic considerations. To gain a more thorough understanding of factors, influencing grain size, growth restriction in copper alloys was investigated both, by accurately determined growth restriction factors from thermodynamic software packages combined with grain size modelling, and experimental studies, using defined casting conditions of standardized grain refiner tests. It was found that the concept of growth restriction is equally adaptable in the copper system, as in the aluminium and magnesium system, however, tends to be affected to a greater extent by impurities, noteworthy oxygen, phosphorus and sulphur, in turn, influencing the nucleation potency of the melt, by in-situ formation of non-metallic inclusions. These factors, affecting grain size transition, found for multiple alloying elements, were successfully clarified by scanning electron microscope analysis and crystallographic evaluation, applying the etch-to-etch matching model. The influence of in-situ formed particles was further studied in standardized copper-based alloys by crystallographic and thermodynamic considerations. Comprehensive fundamental thermodynamic data, noteworthy Gibbs’ free enthalpy of solution, first- and second-order interaction parameter, required for thermodynamic calculations, was determined from semi-empiric thermodynamic models. By combining the results of the etch-to-etch matching model and thermodynamic calculations, the grain refinement mechanism of in-situ formed non-metallic inclusions, acting as nucleation sites, was successfully clarified and applied to several copper-based alloys.