PURPOSE: We reviewed the data from the clinical trials of nutritional supplements for the treatment of age-related cataract and age-related macular degeneration (AMD) to determine future directions of research and treatment. METHODS: Data from the controlled clinical trials are presented and reviewed for potential opportunities for further research into the treatment of cataracts and AMD. RESULTS: Two trials using daily multivitamins/minerals demonstrated a reduction in the progression of nuclear cataract, but increased the risk of posterior subcapsular cataract. For AMD, the Age-Related Eye Disease Study (AREDS) formulation (vitamins C, E, beta-carotene, zinc, and copper) reduced the risk of progression to advanced AMD by 25% at 5 years. Because beta-carotene is associated with increased lung cancer in former smokers, lutein/zeaxanthin could replace beta-carotene and provide an incremental increase in the beneficial effects beyond the effects of the AREDS formulation. In addition, a randomized clinical trial of B vitamins demonstrated a beneficial effect for AMD with the vitamin B complex. CONCLUSIONS: Future evaluation may include additional assessments of nutrients for the treatment of progression of cataract and AMD. A modest reduction would have significant impact as the numbers of persons affected with these two leading causes of blindness are projected to double in the next decade. An important step would be to develop surrogate outcomes to increase efficiency in clinical trials. More detailed phenotyping, especially of AMD, is required as it appears to be not one disease, but a group of diseases. Genotype-phenotype analyses may help to target pathways that are important in AMD.