This chapter introduces and discusses what is meant by the term “set-up error.” The classifications of these errors will be looked at alongside the consequences that can result from the errors if the patient is treated without correction. Set-up errors can occur due to a number of events and are quite commonly due to a combination of small errors or omissions. Classification of set-up errors is essential to take appropriate remedial action; different actions are required depending on if the error is found to be random or systematic. Systematic errors can also be described as treatment preparation errors, as they are usually due to a discrepancy at treatment planning or preparation stage: incorrect instructions given, incorrect markings on patient, or misaligned lasers. Random errors can be described as treatment execution errors, as the error generally occurs during the delivery of a particular treatment, patient or organ motion, incorrect calculation of moves, or wrong immobilisation used.