The background leading to the need for ocular toxicity testing is reviewed. Awareness of side effects of various categories of drugs (e.g., steroids and cataracts) has provided impetus for examination of many categories of compounds including ocular drugs, cosmetics and household chemicals. The standard test (Draize) used for many years in the evaluation of ocular toxicity of many chemicals is being modified or replaced by other procedures. Modifications include volume and/or concentration reductions. Replacements include the use of in vitro systems of either freshly isolated tissues, tissue cultured cells, or non-living systems. The relative predictability of each approach is evaluated with the conclusion that only in vivo testing (albeit using low doses and low volumes) can reflect the full spectrum of potential responses. Each in vitro methodology has at least one drawback relative to in vivo test procedures.