Negative-bias-temperature-instability (NBTI) has become the primary limiting factor of circuit lifetime. In this work, we develop a general framework for analyzing the impact of NBTI on the performance of a circuit, based on various circuit parameters such as the supply voltage, temperature, and node switching activity of the signals etc. We propose an efficient method to predict the degradation of circuit performance based on circuit topology and the switching activity of the signals over long periods of time. We demonstrate our results on ISCAS benchmarks and a 65nm industrial design. The framework is used to provide key design insights for designing reliable circuits. The key design insights that we obtain are: (1) degradation due to NBTI is most sensitive on the input patterns and the duty cycle; the difference in the delay degradation can be up to 5X for various static and dynamic conditions, (2) during dynamic operation, NBTI-induced degradation is relatively insensitive to supply voltage, but strongly dependent on temperature; (3) NBTI has marginal impact on the clock signal.