Although an increasing proportion of head and neck malignancies are treated with non-surgical modalities, when surgery is undertaken an incomplete clearance results in significantly worse prognosis. However, the intraoperative assessment of an adequate margin is difficult. The personal practice of the authors in this review is to attempt margins of 1cm or greater of visible mucosa and 1cm of palpable deep margins. The review goes on to comprehensively explore the various factors influencing adherence to, or deviation from, this decision and the success of resection. As well as covering concepts such as anatomical and histological margins, it discusses the importance of meeting with the histopathologist to review the specimen, particularly in fragmented and poorly oriented tumours as is the case with minimally invasive approaches. Specimen tissue shrinkage may also affect margin analysis, and whilst electrosurgical instruments reduce shrinkage as compared with a steel scalpel (possibly due to thermal injury to tissues) the latter is associated with less tissue distortion of the margin which may affect subsequent analysis. Finally the review discusses the potential future role of molecular analysis of margins. The techniques of epigenetic analysis of tumour markers such as p16 and DAPK as well as using optical techniques of autofluorescence or topical fluorescent agents with high resolution micro-endoscopes may one day help intraoperative delineation of the dysplastic margin at a molecular level. Overall this is a useful and engaging review with appeal to both the generalist and specialist in head and neck surgery.