ABSTRACT: BACKGROUND: The World Health Organization (WHO) Global Program to Eliminate Lymphatic Filariasis relies on mass drug administration (MDA) of two drugs annually for 4 to 6 years. The goal is to reduce the reservoir of microfilariae in the blood to a level insufficient to maintain transmission by the mosquito vector. In 2008, the international medical aid organization Medecins Sans Frontieres (MSF) performed the first round of a MDA in the high-burden area of Asmat district, in Papua, Indonesia. We report the challenges faced in this MDA on a remote Indonesian island and propose solutions to overcome these hurdles in similar future contexts. RESULTS: During the MDA, we encountered difficult challenges in accessing as well as persuading the patient population to take the antifilarial drugs. Health promotion activities supporting treatment need to be adapted and repetitive, with adequate time and resources allocated for accessing and communicating with local, seminomadic populations. Distribution of bednets resulted in an increase in MDA coverage, but it was still below the 80-85% target. CONCLUSIONS: MDA for lymphatic filariasis is how the WHO has planned to eliminate the disease from endemic areas. Our programmatic experience will hopefully help inform future campaign planning in difficult-to-access, high-burden areas of the world to achieve target MDA coverage for elimination of lymphatic filariasis.