Proton beam radiotherapy (PBT) offers great promise in the treatment of a wide variety of cancers owing to the sharp drop-off in radiation dose at a defined point, known as the Bragg peak, beyond which there is no appreciable dose. However, it is also well-understood that PBT is associated with large economic costs, including both capital investment and operating costs. From a medical as well as societal perspective, therefore, it is important to be aware of the economic implications of new technologies such as PBT, and to evaluate the cost effectiveness based on different clinical and treatment scenarios. This review examines PBT from a health economics perspective, evaluating both the design and results of costeffectiveness (CE) studies that have been performed previously. We further examine several salient variables that can affect CE of PBT, including patient, tumor, treatment, and logistical factors. We discuss the implication of technological advances on PBT delivery, and its impact on overall healthcare delivery costs. Additionally, we evaluate the status of economic analyses for PBT and discuss the role of ongoing and future CE studies in better defining the economic role of PBT as part of modern cancer therapy.