Tide and ebb of interest in gastrointestinal tract cytology has followed technical advances in this field over the last 60 years. Cytologic samples can be obtained using gastric lavage, abrasive balloons, mucosal brushing, and fine needle aspiration (under percutaneous image guidance, endoscope and endoscopic ultrasound guidance). These advances now allow simultaneous performance of brushing the abnormal mucosa, obtaining fine needle aspirates and excising mucosal biopsy samples for evaluation. Use of endoscopic ultrasound guided fine needle aspirates now help to obtain diagnosis of submucosal lesions, preoperative staging of gastrointestinal tract malignancies and help determine further management of patients. Such advances have brought pathologists to the forefront of the patient management team for the treatment of gastrointestinal tract lesions. This manuscript reviews the advantages and limitations of each cytology associated technique as well as reviews the salient diagnostic features, differential diagnosis and diagnostic pitfalls of gastrointestinal tract lesions. Finally, it suggests the modalities best suited to obtain diagnosis for various gastrointestinal tract lesions.