This chapter analyzes the approaches to target coenzyme Q derivatives to mitochondria. Coenzyme Q is an essential electron carrier and an important antioxidant in the mitochondrial inner membrane. Manipulating coenzyme Q content within mitochondria may help in understanding its functions and exploring its therapeutic potential. One way to increase the mitochondrial concentration of coenzyme Q is to administer it to isolated mitochondria, cells, or organisms, but the hydrophobicity of native coenzyme Q and its consequent low solubility and bioavailability limit this approach. The hydrophobicity of coenzyme Q is due to the long isoprenoid chain at ring position 6. Less hydrophobic but still active derivatives of coenzyme Q can be made by replacing the carbon chain with more water soluble moieties. The chapter describes the concepts related to synthesis and handling of mitochondria-targeted coenzyme Q derivatives. The chapter also discusses the incorporation of radioactive and stable isotopes into mitochondria-targeted coenzyme Q derivatives. The chapter elaborates the modifying and measuring coenzyme Q redox state. The chapter provides a brief about experiments with mitochondria-targeted coenzyme Q derivatives. The chapter provides an analysis of mitochondrial uptake of mito Q and locationof targeted coenzyme Q derivatives within mitochondria.