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Trachoma, the second leading cause of blindness worldwide, differentially affects the poorest communities, which may have the least access to resources. With the establishment of the Global Elimination of Blinding Trachoma by 2020 (GET 2020) goal, the World Health Organization has set an ambitious target for country programs. The currently recommended surgery for trichiasis/entropion, antibiotics for active disease, facial cleanliness, and environmental change to reduce transmission (SAFE) strategy targets all key elements believed to be necessary for a short- and long-term intervention program. This report reviews the need for a multi-faceted strategy, and the evidence supporting the elements of SAFE. Concerns about the implementation are discussed. Additional research is suggested that will enhance the implementation of the SAFE strategy. In the current climate of significant political and social momentum for trachoma control, the SAFE strategy is a safe bet to accomplish the elimination of blinding trachoma.