APOPO was initiated in response to the global landmine problem. In the mid 1990s it was well recognized that most mine-clearance techniques in use were slow and expensive. The humanitarian community called for an efficient method for the detection of landmines and un-exploded ordnance (UXO) in order to facilitate the repatriation of refugees and distribution of emergency aid, thereby creating the basic conditions for development in a mine-free environment.

In response to this call an analysis of the landmine problem was made with a special focus on sub-Sahara Africa, which is more affected by landmines than any other region in the world. It became clear that landmines pose a structural barrier to any development. Moreover, vulnerable communities remained dependent on imported expertise to address the complex problems of landmine detection and clearance of suspected areas.

The idea of using rodents for mine detection was the outcome of a creative process, in which the goal was set to find an appropriate detector sustainable within the African environment, and enabling empowerment of African communities to reduce dependency on foreign aid. Evidence of olfactory discrimination of explosives by lab rats was found in American scientific publications from the 1970s. APOPO found a suitable rodent species in the Giant African Pouched Rat (Cricetomys gambianus), which is omnipresent in sub-Saharan Africa, has a long life span, and is resilient to most tropical diseases.

APOPO set out to develop an appropriate detection rat technology, based around the Giant African Pouched Rat. The results of a two-year initial research phase strengthened APOPO reasoning to use this species for humanitarian detection tasks in Africa. A group of wild rats were captured and put through a captive breeding program. They were domesticated, and a humane training protocol was developed based on the principles of positive behaviour reinforcement. Once proof of principle was achieved, APOPO transferred the project to Tanzania, to develop the technology together with the African partners in the cultural context the technology would be used in.