Reinforced concrete (RC) frame buildings with masonry infills represent one of the most common structural typologies worldwide. Although, in the past, masonry infills were frequently considered as non-structural elements and their interaction with the structure was neglected, earthquakes occurring over the last decades have demonstrated the important role of these elements in the seismic response of all RC-infilled building typologies. In this regard, the selection of the most suitable numerical modelling approaches to reproduce the hysteretic response of the masonry infills—and their interaction with the RC frames—is still an open issue. To deal with this issue, in this study, a macro-classification based on different available databases of experimental tests on infilled RC frames, is firstly proposed to understand the variability in the infill properties and the corresponding numerical modelling uncertainties. Five masonry infill types are selected as representative for the typical existing configurations in Italy and other Mediterranean countries. Three of those masonry infill types are then selected to carry out a more detailed analysis, namely their numerical modelling validation using experimental testing results, considering and comparing the main formulations available in the literature for the definition of the hysteretic behaviour of infills. From such a comparison, the model that minimizes the prediction error, according to specific features of the selected masonry infill, is identified for each masonry infill type.