Nonlinear circuit simulation in the frequency and time domains is a very important tool for analysis, design, and optimization of high-efficiency switched-mode power amplifiers of Classes D, DE, and E. The advantages are significantly reduced development time and final product cost, better understanding of the circuit behavior, and faster obtaining of the optimum design. It is especially important at very high frequencies, including microwaves, and for MMIC development, where the transistor and circuit parasitics can significantly affect the overall power-amplifier performance. Therefore, it is very important to incorporate into the simulator as accurate a transistor model as possible, to approximate correctly the device behavior, not only at the fundamental frequency, but also at the second and higher harmonics of the operating frequency. In this chapter, the different CAD programs are described to analyze the time-domain and frequency-domain behavior of the switched-mode high-efficiency power amplifiers in different frequency ranges from high frequencies to microwaves, including HB-PLUS and SPICE CAD tools for Class-D and Class-DE circuits and HEPA-PLUS, SPICE, and ADS CAD tools for Class-E circuits. We present and discuss a detailed simulation example of a high-efficiency two-stage 1.75-GHz HBT MMIC power amplifier that uses microstrip transmission lines in the supply and load networks.