The recent improvements in isolation system products have led to the design and construction of an increasing number of seismically isolated buildings worldwide (Ceccoli et al. 1999, Chopra 1995, Kelly 1986, Zou et al. 2010). Similarly, seismic isolation has been extensively used for seismic retrofitting of existing buildings (DeLuca et al. 2001, Mokha et al. 1996). In addition, base isolation concepts are utilized for the protection from shock and vibration of sensitive components of critical facilities such as hospitals, nuclear reactors, industrial and data center facilities. One of the difficulties in the analysis and design of base-isolated systems has been the explicit consideration of the non-linear behavior of the isolators. Another challenge has been the efficient prediction of the dynamic response under future ground motions considering their potential variability as well as competing objectives related to the protection of the superstructure and the minimization of base displacement. The objective of this work is to characterize the performance of base-isolated systems from a reliability point of view. In particular, the case of large scale building models is considered here. Isolation systems composed by rubber bearings are used in the present formulation. The non-linear behavior of these devices is characterized by a biaxial hysteretic model which is calibrated with experimental data (Yamamoto et al. 2009). First excursion probabilities are used as measures of the system reliability.