Published studies of sarcomas using 31P MRS suffer from technical limitations that include absence of localization to regions of interest, resulting in heavy contamination with signals from muscle, and poor resolution. This review has shown that, in spite of their limitations, many of these studies provide important leads to indicate the directions that need to be taken to further develop clinical and biologic uses of MRS. The uniqueness of the metabolic information available in vivo in a noninvasive manner using MRS provides a major stimulus to pursue these directions. In particular, the potential of 31P MRS to predict treatment sensitivity and resistance in individual cases could lead to a very cost-beneficial clinical use of this procedure. 1H-decoupling and NOE-enhancement, implemented in conjunction with dual-tuned surface coils and accurate localization of 31P MR spectra to regions of interest in three dimensions using CSI, have enabled us to overcome the major technical limitations mentioned earlier, broaden the scope of 31P MRS investigations, and obtain more information about the in vivo metabolic characteristics of soft-tissue sarcomas than has heretofore been available. Our approach, which has been fully implemented in a clinical imager, provides a good technical basis from which to examine potential clinical uses of 31P MRS. In particular, we can now rigorously test the hypotheses, derived from preliminary studies in the literature, that initial metabolic features or early treatment-induced changes in PME predict sensitivity of a sarcoma to that particular treatment. To this end, we at Fox Chase Cancer Center, along with investigators at Duke University, the Institute of Cancer Research/Royal Marsden Hospital, Johns Hopkins University, Memorial Sloan-Kettering Cancer Center, St. Georges Hospital Medical School, the University of California at San Francisco, and Wayne State University have initiated an NCI-sponsored cooperative trial to examine the role of 31P MRS in the clinical management of soft-tissue sarcomas and other selected cancers.