Lonidamine induces in murine and human tumor cells severe morphological damage of the mitochondria and other cytoplasmic structures both ‘in vitro’ and ‘in vivo’. Biochemical studies have demonstrated that the drug decreases oxygen consumption and lactate production. The sensitivity of human tumor cells is not related to their histotype. Lonidamine’s effects on mitochondria, glycolysis, pentose phosphate pathway, and aromatase activity are discussed.