In order to establish a D-T fusion reactor as an energy source, it is not enough to have a DT burning plasma, and economical conversion of fusion energy to electricity and/or heat, a large enough margin of tritium breeding and tritium safety must be simultaneously achieved. In particular, handling of huge amount of tritium needs significant efforts to ensure that the radiation dose of radiological workers and of the public is below the limits specified by the International Commission on Radiological Protection (ICRP). In this paper, after the introduction of tritium as a fuel of DT reactors and as a radioisotope of hydrogen, tritium safety issues in fuel cycle and blanket systems are summarized. In particular, in-vessel tritium inventory, the most important and uncertain tritium safety issue, is discussed in detail.