After the World War I, France the new colonial power decided to produce quinine in Cameroon. Many million francs were invested in this undertaking until 1947. As soon as the production of quinine began, the discovery of the chemical antimalarial drugs combined with insecticides (DD.T, Dieldrin, etc.), along with the global campaign of malaria eradication launched by the World Health Organization (WHO) obliged France to abandon its programme. The advances realized until 1958, in Yaoundé and Garoua, the pilot zones of malarial campaign, as well as in different towns were overshadowed by the mosquitoes resistance to insecticides and chemio-resistance of malaria parasite. Despite the new plans undertaken in 1960 by addenda between WHO and Cameroon, Cameroon government was not able to continue the fight against the parasitosis disease. Even if in 1962, the WHO spent 16.1 per cent of its budget to Malaria, its experts who had changed their vocabularly by using the words ‘supression’, ‘eliminination’ or ‘pre-eradication‘, were aware that it was not possible to eradicate malaria not only in Cameroon, but also in the tropical world. This paper stresses on the accumulated errors since the 1950s, notably the lack of knowledge concerning the mosquitoes bio-ecology, along with the lack of sanitary personnels. My objective is to show how the socio-political issues combined with environmental and technical problems constituted an obstacle to the struggle against malaria disease.