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As technology scales, variability in transistor performance continues to increase, making transistors less and less reliable. This creates several challenges in building reliable systems, from the unpredictability of delay to increasing leakage current. Finding solutions to these challenges require a concerted effort on the part of all the players in a system design. This article discusses these effects and proposes microarchitecture, circuit, and testing research that focuses on designing with many unreliable components (transistors) to yield reliable system designs.