Epigenetics has drawn much attention as a mechanism of transcriptional regulation involving modifications to genomic DNA and histone, without changes to nucleotide sequences. Epigenetics is related to various biological phenomena. We defined one of these phenomena as “epigenetic toxicity”, in which chemicals affect epigenetic regulation and result in undesirable effects on living organisms. We then detailed the importance of epigenetics and the need for intensive research. Epigenetics is a mechanism that might explain the long-lasting effects of chemicals in an organism, and the formation of a predisposition to various diseases. Recent significant technological advancement in the study of epigenetics could break through the barrier of the mysterious black box of epigenetic toxicity. However, at present it is difficult to say whether the epigenetic point of view is being fully utilized in the evaluation of chemical safety. In this review, we will first summarize the epigenetic toxicity research field, with examples of epigenetic toxicities and technologies for epigenetic analysis. Following that, we will point out some challenges in which an epigenetic viewpoint may be essential for the evaluation of chemical safety, and we will show some current approaches. We hope this review will trigger a discussion about epigenetic toxicity that will lead to encouraging research advancements.