The relationship between geography and cancer incidence and treatment is a critical area of health outcomes research. Geographical information systems (GIS) are software packages designed to store and analyze data related to geographic locations. Although more commonly associated with the social sciences and urban planning, the use of GIS software in medical research has been increasing. Moreover, since the 1999 establishment of the Geographical Informational Systems Special Interest Group (GISSIG) at the National Cancer Institute, oncology has been at the forefront of GIS-related health research. In this review, we discuss the potential applications and limitations of GIS software in oncology research. Our aims are to help clinicians and policy makers interpret studies generated using GIS, and to help clinical investigators implement GIS in future research.