PET with time-of-flight (TOF) capability has been shown to provide a better reconstructed image compared to conventional positron tomography. The increase in SNR mainly depends on the size of the patient being imaged Conti (2009), the intrinsic resolution of the detector and the resolution of the TOF. In TOF-PET approach, for each detected event, the measurement of the time of flight difference between the two 511 keV photons provides an approximate value for the position of the annihilation. The approximation is directly limited to the capability of measuring the arrival time of the two photons. In the 1980s, TOF-PET were built with an achieved timing resolution of 500 ps Moses (2007). At that time, the electronics available drastically reduced the performances of the TOF-PET. Nowadays, electronics operating in the GHz range is routine and the application-specific integrated circuits (ASIC) are commonly used Ollivier-Henry et al. (2007). The ASIC needs to include a high-precision time-to-digital converter (TDC) for each detector element to reach the required time resolution(i.e., less than 100 ps)with good stability. The objective of this chapter is to review the state-of-the-art of the TDC techniques and to select proper architecture for PET imaging systems. Both the conventional TDCs and the novel TDCs are presented. The comparison of the TDC architecture is given as well.