Diseases caused by parasitic infections are responsible for considerable morbidity and mortality. The progress in the development of vaccines against parasite infections tends to be slow and the epidemiological control of diseases is unsatisfactory. Currently, chemotherapy remains an essential component of clinical management and disease control programs. In the past 20 years, there was a significant increase in our basic knowledge about structure and biochemical functions of parasites. Several studies to identify unique metabolic pathways and key enzymes for parasite survival are in progress, which may support the development of novel target-based drugs. The mitochondrial respiratory chain of parasites typically shows greater diversity compared with host animals; including the electron transport complexes and their related enzymes; tRNA import, as well as the synthesis of fatty acids, pyrimidines and ubiquinones. These unique aspects may represent promising targets for chemotherapy. This review presents a compilation about the knowledge and understanding of the action of therapeutic agents on mitochondria from parasites and their future perspectives.