Toxicity of food components is now under intense scrutiny as the public has become increasingly concerned about the safety of our food supply. Products of lipid oxidation and thermal degradation have long been suspected as potential toxins when consumed in the diet, and numerous changes induced by lipid oxidation products have been reported. However, animals have extensive endogenous protection mechanisms throughout the gastrointestinal system in the liver, and in all tissues, so presumed toxicity must be differentiated from normal physiological metabolism and detoxification. This article reevaluates whether and how oxidizing lipids consumed in foods may or may not be toxic, with focus on levels ingested, modification during digestion, absorption vs action only in the gut, physiological processing, effects of other diet components, and differentiating normal responses from actual toxicity. Recommended guidelines for future research are included.