Pancreaticoduodenectomy (PD) is the standard surgical treatment for tumors of the pancreatic head, proximal bile duct, duodenum and ampulla, and represents the only hope of cure in cases of malignancy. Since its initial description in 1935 by Whipple et al, this complex surgical technique has evolved and undergone several modifications. We review three key issues in PD: (1) the initial approach to the superior mesenteric artery, known as the artery-first approach; (2) arterial complications caused by anatomic variants of the hepatic artery or celiac artery stenosis; and (3) the extent of lymphadenectomy.