The diagnosis and management of pancreatic cystic lesions remains a challenging area in gastroenterology. Differentiating benign from premalignant or premalignant from malignant cysts is complicated by the large overlap in morphologic, chemical, and clinical characteristics. Imaging alone is insufficient to accurately characterize these lesions. Cyst aspiration and fluid analysis has therefore become a major research focus through which our ability to characterize pancreatic cystic lesions has improved, although accuracy is often still lacking. Future work with molecular analysis of cyst fluid, direct cystoscopy, and confocal laser endomicroscopy will likely further enhance the diagnostic accuracy of these lesions.