The technologies available to identify anatomical structures (including radiotherapy target and normal tissue 'volumes'), and to deliver dose accurately to these volumes, have improved significantly in the past decade. However, the ability of clinicians to identify volumes accurately and consistently in patients still suffers from uncertainties that arise from human error, inadequate training, lack of consensus on the derivation of volumes and inadequate characterisation of the accuracy and specificity of imaging technologies. Inadequate volume definition of a target can result in treatment failure and, consequently, disease progression; excessive volume may also lead to unnecessary patient injury. This is a serious problem in routine clinical care. In the context of large multi-centre clinical trials, uncertainty and inconsistency in tissue-volume reporting will be carried through to the analysis of treatment effect on outcome, which will subsequently influence the treatment of future patients. Strategies need to be set in place to ensure that the abilities and consistency of clinicians in defining volumes are aligned with the ability of new technologies to present volumetric information. This review seeks to define the concept of volumetric uncertainty and propose a conceptual model that has these errors evaluated and responded to separately. Specifically, we will explore the major causes, consequences of, and possible remediation of volumetric uncertainty, from the point of view of a multidisciplinary radiotherapy clinical environment.