In the past, the chemical industry in Japan has been the cause of a number of major industrial accidents. Subsequent to each accident, specific lessons have been learned. These lessons learned have been implemented in terms of safety education of the employees and/or safety measures of the equipment and facilities resulting in a rapid decrease of corresponding accident frequencies. In this paper, we summarized both recent and past major accidents caused by chemical substances in fixed installations in Japan. Case studies show that runaway reactions are among the main causes of major accident occurrences in the chemical process industry in Japan. A recent fatal poisoning accident caused by H2S gas generated during maintenance work again highlights the necessity of adequate safety management in a chemical factory. Therefore, even if hazard evaluation of chemical substances and chemical processes is necessary to prevent runaway reactions, human error is also an important factor contributing to reaction hazards [Wakakura, M. (1997) Human factor in chemical accidents, J. Safety Eng. High Press. Gas. Safety Inst. Japan, 34, 846].