Damage to non-structural components during recent earthquake events, such as the Darfield earthquake in New Zealand (2010) have confirmed the need to better address the interaction between a structure and its non-structural components. This paper aims to numerically investigate the seismic behaviour of a typical newly designed reinforced concrete multi-storey frame building with and without the interaction due to cladding panels. This interaction is investigated by means of non-linear static and dynamic analyses for common typologies of cladding systems. A seismic risk assessment analysis is also presented in order to develop fragility functions based on damage limit states for cladding connection. These are used for assessing the probability of damage of cladding systems after earthquake events of varying intensity. Results confirm the high influence of cladding systems upon the seismic performance of multi-storey buildings. Also revealed is the significant variation in possible levels of cladding damage throughout a building. Further investigations are going to be developed, refining the use of fragility functions associated to innovative low damage cladding solutions.