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Reliability is an essential scientific and technological domain intrinsically linked with system integration. Nowadays, semiconductor industries are confronted with ever-increasing design complexity, dramatically decreasing design margins, increasing chances for and consequences of failures, shortening of product development and qualification time, and increasing difficulties to meet quality, robustness, and reliability requirements. The scientific successes of many micro/nano-related technology developments cannot lead to business success without innovation and breakthroughs in the way that we address reliability through the whole value chain. The aim of reliability is to predict, optimize, and design upfront the reliability of micro/nanoelectronics and systems, an area denoted as “Design for Reliability (DfR)”. While virtual schemes based on numerical simulation are widely used for functional design, they lack a systematic approach when used for reliability assessments. Besides this, lifetime predictions are still based on old standards assuming a constant failure rate behavior. In this chapter, we will present the reliability and failures found in solid-state lighting systems. It includes both degradation and catastrophic failure modes from observation toward a full description of its mechanism obtained by extensive use of acceleration tests using knowledge-based qualification methods.