Adrenal pathologies have various patterns of presentation, depending on their endocrine functional hormone excess and oncologic potential. Evaluation of the patient with disease of the adrenal gland requires a thorough understanding of physiology and proper application of conventional and molecular (isotopic) imaging and biochemical testing to guide therapy. Selecting the best approach for surgical resection of an adrenal mass requires consideration of a multitude of factors, including the size of the tumor and degree of suspicion of malignancy. Tumors greater than 6 cm in size, because of the malignant potential, and those with features worrisome for adrenocortical carcinoma (ACC), should be resected by an open en bloc approach [1–3]. Other factors influencing the therapeutic approach include laterality of the disease, presence of multiple or extra-adrenal tumors, additional intra-abdominal disease, distant metastases, history of prior abdominal surgery, patient’s body habitus, and the operating surgeon’s experience.