A large part of the building stock in seismic-prone areas worldwide are masonry structures that have been designed without seismic design considerations. Proper seismic assessment of such structures is quite a challenge, particularly so if their response well into the inelastic range, up to local or global failure, has to be predicted, as typically required in fragility analysis. A critical issue in this respect is the absence of rigid diaphragm action (due to the presence of relatively flexible floors), which renders particularly cumbersome the application of popular and convenient nonlinear analysis methods like the static pushover analysis. These issues are addressed in this paper that focusses on a masonry building representative of Southern European practice, which is analysed in both its pristine condition and after applying retrofitting schemes typical of those implemented in pre-earthquake strengthening programmes. Nonlinear behaviour is evaluated using dynamic response-history analysis, which is found to be more effective and even easier to apply in this type of building wherein critical modes are of a local nature, due to the absence of diaphragm action. Fragility curves are then derived for both the initial and the strengthened building, exploring alternative definitions of seismic damage states, including some proposals originating from recent international research programmes.