Background: The monoexponential water T 2 (T 2-mono) is a proven biomarker of disease activity in neuromuscular disorders (NMDs). However, it lacks specificity, being elevated in the presence of several pathological processes and pathomorphological alterations in the muscle tissue. Purpose: To investigate the multiexponential behavior of the water T 2-relaxation in the skeletal muscle of NMD patients, aiming to identify more sensitive and specific biomarkers of disease activity. Study Type: Retrospective case-control. Population: Thirty Duchenne muscular dystrophy and 114 inclusion body myositis patients and 55 control subjects. Field Strength/Sequence: 3T/Single-voxel proton spectroscopy (1 H-MRS) and multispin-echo (MSE) imaging. Assessment: Water T 2-decay curves generated from 1 H-MRS data acquired at 14 echo-times were fitted to mono-and biexponential models and the adjusted R 2 of each fit was computed. Additionally, T 2 spectra were generated from a regularized inverse Laplace transform. For comparison, water T 2 maps were generated from the MSE data. The performances of the different variables at identifying patients were assessed via receiver operating characteristic (ROC)-curve analysis. Statistical Tests: Chi-square, Kruskal-Wallis, and Mann-Whitney with Bonferroni correction for multiple comparisons. Results: T 2-mono was elevated in patients (P<0.05), but could not distinguish inclusion body myositis (IBM) from Duchenne muscular dystrophy (DMD). While 79% of IBM data presented a biexponential behavior, this was only 16% and 10% for DMD and control data, respectively (P<0.05). All T 2 spectra presented an intermediate-T 2 peak characterized by an elevated T 2 in patients (P<0.05) and by a relative fraction that was abnormally smaller in IBM patients (P<0.05). Also, a long-T 2 peak was exclusively observed in IBM patients. A combination of T 2-spectrum variables performed best at identifying patients. Data Conclusion: T 2 spectra not only provided more sensitive and specific markers of disease presence than the T 2-mono , but also allowed distinguishing IBM from DMD patients. This must reflect distinct predominant pathological alterations between these diseases, suggesting that these markers provide additional pathophysiological/histopathological information that are missing from T 2-mono. Level of Evidence: 3 Technical Efficacy Stage: 3