In today's systems, analog and mixed-signal (AMS) circuits are tightly interwoven with HW/SW systems and the application. Hence, a verification of the AMS part alone is not sufficient any more, in particular considering its application in Cyber-Physical Systems. In order to guarantee 'first time right', the accuracy of the models, the validation of the application fitness, and in changing, uncertain environments will become at least as important. In this paper we discuss and give an overview of methods that strive for validation of AMS systems with increased coverage. We in particular focus modeling, verification and validation of uncertainties in the context of Cyber-Physical Systems.