Over the years many techniques have been devised for the measurement of tissue oxygenation (oximetry). Oximetry using polarographic needle electrodes has long been considered a gold standard. Nuclear Magnetic Resonance (NMR) based oximetry uses exogenously administered reporter molecules such as perfluorocarbons to quantitatively interrogate oxygen tension (pO2). This technique has been successfully used in vivo in the preclinical setting and shows promise for clinical applications. NMR pO2 reporter molecules display a linear dependence of the spin lattice relaxation rate on pO2, which forms the basis of this technique. Physical principles of spin lattice relaxation of pO2 reporter molecules and the pO2 dependence of relaxation rate are discussed in this review. Practical considerations for choice of reporter molecules for in vivo measurements, general methodology and new developments are also described.