Phototoxic chemicals produced by plants have been studied in a number of contexts, most notably as protective agents against mammalian and insect herbivores. Although there are commonalities in the responses of these two groups of herbivores to plant phototoxins, there are differences as well. Whereas a greater range of chemical classes has been demonstrated to display phototoxicity against insects, considerably more information is available on symptomology of phototoxicity and mechanisms of action in mammals. The commonalities include alterations in behavior following ingestion, notably photophobia, disruption of integumentary integrity following contact or ingestion, and metabolic detoxification following ingestion, in the case of furanocoumarins involving cytochrome P450 monooxygenases. Not yet known to exist in insects are phototoxin-mediated effects on sensory (particularly visual) systems and phototoxicity resulting from abnormal chlorophyll metabolism. In order to gain greater understanding of the ecological significance of phototoxin-mediated plant defense against both insects and mammals, there is a need for more studies centered on natural associations.