This thesis addresses the challenge of designing reliable and energy-efficient subthreshold flip-flops. A dual-clock-phase flip-flop (TG-FF) and a single-clock-phase flip-flop (SP-FF) configurations are considered and their gradual design modifications are reported towards perfecting their yields at minimum cost in terms of energy consumption. In addition, the two optimized flip-flop designs are compared based on the criteria of static and dynamic energy consumptions, delay, and reliability in face of PVT variations.A 65 nm and a newer 28 nm CMOS technology kit were used during the course of this work. Multi-threshold MOSFETs and transistor sizing technique were incorporated for yield optimization. In general we were able to increase the flip-flops reliabilities to 100% at the nominal temperature and power supply condition, and in the worst-case around 90% in the extreme cold and -10% noise on the power supply. We also prove the overall superiority of the SP-FF compared to TG-FF. i Acknowledgment First and foremost, I would like to express my deep and sincere gratitude to my supervisor Professor Maitham Shams for the continuous support, understanding, kindness, and great guidance. During my studies, he not only helped me in my research but also he taught me in my life.