The combined effects of sunlight and metabolites/drugs are recognized to be a major health hazard. The immediate cutaneous phototoxic effects are manifested as sunburn, acute inflammation and hyper-pigmentation. The chronic exposure results in a number of changes in skin such as wrinkling, atrophy altered pigmented macule, dilation of superficial blood vessels in skin, actinic keratoses and cancer. Examples of ocular phototoxicity are cataract, macular degeneration and corneal opacity. Under certain diseases conditions metabolites e.g. porphyrins, which accumulate in blood or tissues are photosensitive. Some of the commonly administered drugs as well as chemicals present in our environment are also photosensitive. Biological responses to photochemical reactions are mediated by one or more of reactive oxygen species, viz. singlet oxygen, superoxide, hydrogen peroxide, hydroxyl radical; alternatively it may involve direct interaction activated photosensitizer with biomolecules. Under normal conditions these species are scavenged by enzymes e.g. superoxide dismutase, catalase, peroxidase and antioxidant such as ascorbic acid, vitamin E, glutathione etc. However if the defense mechanisms are not sufficient to scavenge the reactive species, harmful effects will occur. We have reviewed here the cutaneous inflammatory reactions occurring under a variety of conditions. These have been illustrated using our findings with the naturally occurring photosensitizers, (pheomelanin and porphyrins), cosmetic and food additives (rose bengal and erythrosine) and drugs (psoralens). In view of these observations the mechanistic approach towards the understanding of the photoinduced cutaneous reactions has been discussed.