Normally light transmission through the eye is benign and serves to direct vision and circadian rhythm. However, with very intense light exposure, or with ambient light exposure to the aged eye and/or young or adult eye in the presence of light-activated (photosensitizing) drugs or dietary supplements, cosmetics, or diagnostic dyes, light can be hazardous, leading to blinding disorders. Light damage to the human eye is avoided because the eye is protected by a very efficient antioxidant system and the chromophores present absorb light and dissipate its energy. After middle age, there is a decrease in the production of antioxidants and antioxidant enzymes and an accumulation of endogenous chromophores that are phototoxic. The extent to which a particular exogenous photosensitizing substance is capable of producing phototoxic side effects in the eye depends on several parameters, including (1) the chemical structure; (2) the absorption spectra of the drug; (3) binding of the drug to ocular tissue (lens proteins, melanin, DNA); and (4) the ability to cross blood-ocular barriers (amphiphilic or lipophilic). For instance, compounds that have either a tricyclic, heterocyclic, or porphyrin ring structure and are incorporated into ocular tissues are potentially phototoxic agents in the eye. The extent to which these substances might damage the eye (photoefficiency) can be predicted using in vitro and photophysical techniques. With simple, inexpensive testing, compounds can be screened for their potential ocular phototoxicity at the developmental stage. It may be that a portion of the molecule can be modified to reduce phototoxicity while leaving the primary drug effect intact. Preclinical safety testing may prevent ocular side effects that can range from mild, reversible blurred vision to permanent blindness.