Among all structures, high-rise buildings pose specific design challenges with respect of fire safety for a number of reasons, in particular the evaluation of both the fire development (fire action) and response of the structural system to fire (structural behaviour). In relation to the fire action, large compartments and open hallways often present in modern high-rise buildings don’t let themselves to be designed within compliance to current codes and standards. A comprehensive analysis of the fire environment is required to understand the fire dynamics in these cases. A Computational Fluid Dynamic (CFD) model allows a quite accurate representation of realistic fire scenarios, because it takes into account the distribution of fuel, the geometry, the occupancy of individual compartments and the temperature rise in structural elements that are located outside the tributary area of fire scenario. In relation to the structural behaviour under fire, the passive fire resistance of structural elements and the intrinsic robustness of the system are the only measures to rely on in order to maintain the structural integrity of the building during and after the fire and avoid major economic losses due to structural failures and prolonged inoperability of the premises. Disproportionate damages induced by fire can be avoided with a proper design of the structure, aimed at reducing the vulnerability of the elements to fire (i.e. their sensitivity to fire) or at increasing the robustness of the structural system (i.e. its sensitivity to local damages).