This chapter introduces a new method for the analysis and optimisation of reliability as an integrated part of the design process of electronic circuits and systems. It bases itself on the analysis of the susceptibility of failure mechanisms in components as a function of the combinations of external stress factors (stressor-sets). The chapter describes the background of stressor-susceptibility analysis, the need for this analysis and the way this method is used for high-level design and optimisation of electronic circuits. The theory is illustrated using the example of secondary breakdown in a (power) bipolar semiconductor, which can be applied, for instance, in 'smart power' designs. The methodology introduced can also be applied in systems of non-electronic and/or mixed nature.