Humidifier disinfectant damages caused by the misuse of humidifier disinfects, such as polyhexamethylene guanidine (PHMG), resulted in chemical disasters in South Korea in 2011. About four million people were exposed to humidifier disinfectants (HDs) in the 17 years between 1994 and 2011. Although fatal lung damage was initially reported, investigations into the victims’ injuries revealed that the damage was not limited to the lungs, but that systemic damage was also confirmed. Considering the spread of HD from the lungs to the whole body, the toxic effects of PHMG from reactive oxygen species (ROS), NOTCH signaling pathways, and mitochondrial dysfunction resulted in endothelial damage in the lungs, blood vessels, liver, kidneys, bone marrow, nerves, and muscles. The main toxic mechanisms involved in HD damage may be the NOTCH pathway and mitochondrial damage. There are many case reports which include neurologic disorders (ADHD, depression, posttraumatic stress disorder), muscular disorder (exercise intolerance, myalgia), energy metabolism disorder (chronic fatigue syndrome), and immunologic disorder (rheumatoid arthritis) in HDs victims. These case reports involve multi-system involvement in HDs victims. Further well-designed study is needed to clarify whether mitochondrial dysfunction is associated with multi-organs involvement in HDs victims.