In July 1997, on the occasion of his visit to Côte d'Ivoire, Dr Hiroyoshi Nakajima, the then Director-General of WHO, encountered the debilitating tropical disease that destroys the skin of its victims: Buruli ulcer. He then announced the deployment of a coalition of international efforts against Buruli ulcer.

With the financial support from the Nippon Foundation, Tokyo, Japan, WHO established the GBUI in February 1998 to coordinate Buruli ulcer control and research efforts. In July 1998, WHO organized the first international conference on Buruli ulcer control and research. This conference marked a significant first step in drawing the attention of the world to the suffering caused by this neglected disease and led to the Yamoussoukro Declaration. In his speech during the conference, Dr Nakajima stated:

"I decided to place emphasis on the fight against Buruli ulcer for the following reasons. In the 21st century, where infectious diseases are concerned, the world will have to find the means both to control major long-standing scourges such as tuberculosis and malaria, and also to deal effectively with emerging diseases such as Buruli ulcer. I am convinced that these two different sorts of challenges will have to be tackled simultaneously. If we fail to do so, the prevalence of infectious diseases as a whole is likely to increase worldwide, and the severity of specific diseases may well increase too."

Since then a number of activities have been carried out at both international and national levels to improve control and accelerate research. More than 40 nongovernmental organizations, research institutions, and foundations are now participating in the Initiative. Nonetheless, Buruli ulcer remains a neglected disease and much work, at all levels, needs to be done to improve prospects for control. Supported by an Advisory group, this Initiative has drawn together global expertise and led mobilization of needed resources.

In May 2004, the World Health Assembly adopted a resolution on Buruli ulcer which called for increasing surveillance and control, and for intensified research to develop tools to diagnose, treat and prevent the disease.

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^{Resolution WHA57.1 Surveillance and control of Mycobacterium ulcerans disease (Buruli ulcer). In: Fifty-seventh World Health Assembly, Geneva, 17–22 May 2004. Resolutions and decisions. Geneva, World Health Organization, 2004 (WHA57/2004/REC/1):1–2.}