The geometric precision of radiotherapy treatments must increase if the objectives of dose escalation and increased disease control are to be achieved. There are multiple strategies for increasing the geometric precision of a radiotherapy treatment system, including immobilization and setup aids for reducing random and systematic components of setup errors and organ motion alike. Alternatively, more complex strategies can be implemented based on additional information acquired over the course of treatment. Generally, these strategies can be divided into two categories: off-line and on-line. The strategies that are implemented in the clinic must consider the required geometric precision for a given treatment. From this specification, it is possible to select the appropriate strategies and approaches. The cost associated with each approach must also be considered. Once a system for delivery has been designed, the residual uncertainties must still be considered in the planning process. Parallel to the development of strategies for reducing uncertainty, progress is being made in better relating these residual uncertainties to margins for use in treatment planning. This article reviews advances in reducing uncertainty.