The attributes of and challenges in the recently suggested probabilistic design for reliability (PDfR) concept, and the role of its major constituents - failure oriented accelerated testing (FOAT) and physically meaningful predictive modeling (PM) - are addressed, advanced and discussed. The emphasis is on the application of the powerful and flexible Boltzmann-Arrhenius-Zhurkov (BAZ) model, and particularly on its multi-parametric aspect. The model can be effectively used to analyze and design optoelectronic (OE) devices and systems with the predicted, quantified, assured, and, if appropriate and cost-effective, even maintained probability of failure in the field. The numerical example is carried out for an OE system subjected to the combined action of the ionizing radiation and elevated voltage as the major stimuli (stressors). The measured leakage current is used as a suitable characteristic of the degree of degradation. It is concluded that the suggested methodology can be accepted as an effective means for the evaluation of the operational reliability of the aerospace electronics and OE systems and that the next generation of qualification testing (QT) specifications and best practices for such systems could be viewed and conducted as a “quasi-FOAT,” a sort of an “initial stage of FOAT” that adequately replicates the initial non-destructive segment of the previously conducted comprehensive “full-scale” FOAT.