Technological developments in image-guided radiotherapy systems have introduced new considerations to the treatment-planning process. These include more rational assessment and reduction of treatment margins; adaptation of treatment plans according to information gathered as treatment progresses; and facilitation of treatments involving the delivery of large, highly focused doses of radiation to tumors. We examine the performance of different treatment-room image-guidance systems in terms of target position accuracy; such information is important for determining treatment margins and deciding on an appropriate correction strategy. Some clinical situations may warrant a modification to a patient's treatment plan part way through a course of treatment, such as tumor shrinkage in response to treatment and daily organ variation. We discuss the challenges and review proposed strategies for treatment-plan adaptation. Image guidance in combination with 3-dimensional conformal and intensity-modulated radiotherapy has provided the tools for clinical trials of single-dose and hypofractionated treatment as an alternative to standard fractionation. We discuss the clinical realization of this treatment paradigm in various disease sites.