Near-threshold computing (NTC) has significant role in reducing the energy consumption of modern very large-scale integrated circuits designs. However, NTC designs suffer from functional failures and performance loss. Understanding the characteristics of the functional failures and variability effects is of decisive importance in order to mitigate them, and get the utmost NTC benefits. This chapter presents a comprehensive cross-layer reliability analysis framework to assess the effect of soft error, aging, and process variation in the operation of near-threshold voltage caches. The objective is to quantify the reliability of different SRAM designs, evaluate voltage scaling potential of caches, and to find a reliability-performance optimal cache organization for an NTC microprocessor. In this chapter, the soft error rate (SER) and static noise margin (SNM) of 6T and 8T SRAM cells and their dependencies on aging and process variation are investigated by considering device, circuit, and architecture-level analysis.