This article reviews the indications for a muscle biopsy, and then gives a step-by-step description of the processes of muscle selection through to interpreting the biopsy report. The article aims to aid the clinician in preparing for a muscle biopsy procedure to avoid common pitfalls and obtain optimal results from this minimally invasive procedure. The basic anatomic structure of normal muscle is reviewed to provide a foundation for understanding common patterns of pathologic change observed in muscle disease and common and disease-specific histopathologic findings are presented, focusing on a select group of neuromuscular diseases.