African trypanosomes are parasitic protozoa of the order of Kinetoplastida, which cause sleeping sickness and nagana. Trypanosomes are not only of scientific interest because of their clinical importance, but also because these protozoa contain several very unusual biological features, such as their special energy metabolism. The energy metabolism of Trypanosoma brucei differs significantly from that of its host, not only because it comprises distinct enzymes and metabolic pathways, but also because some of the glycolytic enzymes are localized in organelles called glycosomes. Furthermore, the energy metabolism changes drastically during the complex life cycle of this parasite. This review will focus on the recent advances made in understanding the process of ATP production in T. brucei during its life cycle and the consequences of the special subcellular compartmentation.