Gallbladder cancer (GBC) is the most common biliary tract cancer worldwide and its incidence has significant geographic variation. A unique combination of predisposing factors include genetic predisposition, geographic distribution, female gender, chronic inflammation, and congenital developmental abnormalities. Today, incidental GBC is the most common presentation of resectable gallbladder cancer and surgery (minimally invasive or open) remains the only curative treatment available. Encouragingly, there is an important emerging role for systemic treatment for patients who have R1 resection or present with Stage III-IV. In this chapter, we describe the epidemiology, pathogenesis, and a systematic approach to indications for surgery, systemic treatment, and prognosis.