Magnetic resonance spectroscopy (MRS) has been most extensively applied to the study of animal models and not humans. The major reason for this extensive animal research is due to the nature of the early magnetic resonance high-field magnets, which only permitted the study of isolated cells, tissues, or small animals. However, equally important was the necessity of using animal models in the investigation of both the MRS technique itself and the actual biochemistry and physiology it interrogates. The advantages and disadvantages of various experimental models for magnetic resonance spectroscopy (MRS) research are presented, along with guidelines for choosing an appropriate model for a given experimental requirement.