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Accurate diagnosis of gastrointestinal neuromuscular diseases requires full thickness biopsy for adequate histologic evaluation of the enteric neuromuscular and ancillary cells. Historically, this has been achieved by surgical approaches. An overview of procedure evolution and current techniques of endoscopic full thickness biopsy (EFTB) for diagnosis of gastrointestinal neuromuscular disorders will be presented.Emergence and advancement of endoscopic full thickness resection techniques has offered a less invasive, nevertheless an effective modality of tissue acquirement. Recently, clip-assisted close-then-cut EFTB has been utilized in clinical practice under research protocol. Early experience has shown that this technique provides an adequate full-thickness specimen including the myenteric plexus and ganglia cells, with acceptable safety profiles.EFTB is a promising means in diagnosing the nature of the disease and guiding therapy. Available animal and human studies have shown the noninferiority of endoscopic methods to surgical ones in term of adequacy of tissue samples, while potentially decreasing the risk and occurrence of complications. Further large prospective studies are needed to assess its efficacy, safety and impacts on patient's outcomes.