Malaria endemicity and epidemiology in Tanzania is changing rapidly as a result of changes in climatological, topographical and vector related factors. Malaria is now prevalent in previously malaria free mountainous areas, such as Muheza, Lushoto, Babati, Hanang and Loliondo Districts where records show dramatic changes in the incidence of and endemicity of malaria in the past five decades. The observed malaria epidemics in Tanzania were also greatly enhanced by a rapid increase in immigrants into and/or from malarious areas and by deforestation. Changes in mosquito host-preference, increased human socio-economic activities, and the wide self medication practices and drug resistance are also likely to have played important roles in malaria epidemics in Tanzania. This overview explores and discusses the contribution of the above-mentioned factors to malaria epidemics in the past five decades.