Some types of organochlorides have significant toxicity to plants or animals, including humans. Dioxins, produced when organic matter is burned in the presence of chlorine, and some insecticides such as DDT are persistent organic pollutants which pose dangers when they are released into the environment. For example, DDT, which was widely used to control insects in the mid 20th century, also accumulates in aquatic food chains. Because the body is not able to break down or dispose of it, and it interferes with calcium metabolism in birds, there were severe declines in some bird predator populations.

When chlorinated solvents, such as carbon tetrachloride, are not disposed of properly, they accumulate in groundwater. Some highly reactive organochlorides such as phosgene have even been used as chemical warfare agents.

However, the presence of chlorine in an organic compound does not ensure toxicity. Many organochlorides are safe enough for consumption in foods and medicines. For example, peas and broad beans contain the natural chlorinated plant hormone 4-chloroindole-3-acetic acid (4-Cl-IAA);[8][9] and the sweetener sucralose (Splenda) is widely used in diet products. As of 2004, there were at least 165 organochlorides approved worldwide for use as pharmaceutical drugs, including the natural antibiotic vancomycin, the antihistamine loratadine (Claritin), the antidepressant sertraline (Zoloft), the anti-epileptic lamotrigine (Lamictal), and the inhalation anesthetic isoflurane.

Rachel Carson brought the issue of DDT pesticide toxicity to public awareness with her 1962 book Silent Spring. While many countries have phased out the use of some types of organochlorides such as the US ban on DDT, persistent DDT, PCBs, and other organochloride residues continue to be found in humans and mammals across the planet many years after production and use have been limited. In Arctic areas, particularly high levels are found in marine mammals. These chemicals concentrate in mammals, and are even found in human breast milk. Males typically have far higher levels, as females reduce their concentration by transfer to their offspring through breast feeding