Power consumption and soft-error tolerance have become major constraints in the design of DSM CMOS circuits. With continued technology scaling, the impact of these parameters is expected to gain in significance. Furthermore, the design complexity continues to increase rapidly due to the tremendous increase in number of components (gates/transistors) on an IC every technology generation. This research describes an efficient and general CAD framework for the optimization of critical circuit characteristics such as power consumption and soft-error tolerance under delay constraints with supply/threshold voltages and/or gate sizes as variables. A general technique called Delay-Assignment-Variation (DAV) based optimization was formulated for the delay-constrained optimization of directed acyclic graphs. Exact mathematical conditions on the supply and threshold voltages of circuit modules were developed that lead to minimum overall dynamic and static power consumption of the circuit under delay constraints. A DAV search based method was used to obtain the optimal supply and threshold voltages that minimized power consumption. To handle the complexity of design of reliable, low-power circuits at the gate level, a hierarchical application of DAV based optimization was explored. The effectiveness of the hierarchical approach in reducing circuit power and unreliability, while being highly efficient is demonstrated. The usage of the technique for improving upon already optimized designs is described. An accurate and efficient model for analyzing the soft-error tolerance of CMOS circuits is also developed.