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Mice with an under\u2010 or overexpression of enzymes involved in high\u2010energy phosphoryl transfer (\u223cP) are particulary attractive for <jats:italic>in vivo<\/jats:italic> MR spectroscopy studies as the substrates of these enzymes are metabolites that are visible in MR spectra. This review provides a brief overview of the strategies used for generation and study of genetically altered mice and introduces the reader to some practical aspects of <jats:italic>in vivo<\/jats:italic> MRS studies on mice. The major part of the paper reviews results of <jats:italic>in vivo<\/jats:italic> MRS studies on transgenic mice with alterations in the expression of enzymes involved in \u223cP metabolism, such as creatine kinase, adenylate kinase and guanidinoacetate methyl transferase. The particular metabolic consequences of these enzyme deficiencies in skeletal muscle, brain, heart and liver are addressed. Additionally, the use of \u223cP systems as markers of gene expression by MRS, such as after viral transduction of genes, is described. Finally, a compilation of tissue levels of metabolites in skeletal muscle, heart and brain of wild\u2010type and transgenic mice, as determined by <jats:italic>in vivo<\/jats:italic> MRS, is given. During the last decade, transgenic MRS studies have contributed significantly to our understanding of the physiological role of phosphotransfer enzymes, and to the view that these enzymes together build a much larger metabolic energy network that is highly versatile and can dynamically adapt to intrinsic genotoxic and extrinsic physiological challenges. 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