Interpreting a muscle biopsy requires enough experience to group together the pathological findings to arrive at a proper diagnosis. Because histological changes may sometimes be unequivocal or subtler, pathologists need a systematic approach to evaluate the abnormal findings seen in biopsies. Pathologists should not simply tell the clinician whether or not myopathic or neuropathic change exists; they also should help the clinician reach the most probable diagnosis. Once the myopathology is defined, the clinical information is essential for the diagnostic correlation. Pathologists may reach the diagnosis by only looking at a hematoxylin and eosin (H&E) section; however, sometimes additional stains are required. In this chapter, we describe a simple approach for muscle biopsy interpretation, and we provide illustrations of the most common pathological findings.