Gallbladder cancer (GBC) is an aggressive disease with a dismal prognosis and resistance to chemotherapy. Due to difficulties in early diagnosis of GBC, about 90% of patients are detected at advanced stages with palliative care being the only viable option. While surgery remains the mainstay treatment for early GBC, most patients who undergo surgical resection present with high degrees of recurrence. Unfortunately for many patients, surgical resection is not considered a possibility due to the time at which they are diagnosed. Adjuvant therapies in the form of radiation and/or embolization of the tumor have been probed for the disease with moderate success. While there have been multiple studies (both retrospective and pooled analysis) that suggest an added advantage of combining adjuvant therapy with surgical resection, data from prospective studies is limited. Interestingly, GBC affects women, American Indian, Alaska Native, and black people, and certain Asian ethnic groups in peculiar geographic locations such as Chile, India, China more than other groups elsewhere. These disparities in gender and ethnicities demonstrate the need for better understanding of underlying genetic events of GBC so that molecularly targeted therapies could be developed to provide hope for improving treatment response and better outcome. However, for GBC not much progress has been made mainly due to the lack of understanding of molecular pathogenesis of this disease. This article presents a review of literature focused on molecular and genetic alterations in GBC, and as to how effective targeted therapeutic strategies can be developed with demonstrated survival benefit.