There is a paucity of literature on quality of life (QoL) in patients with oral potentially malignant disorders (OPMDs) despite these conditions being relatively common, chronic, and potentially debilitating. The aim of this paper is to systematically review the literature on QoL in patients with OPMDs. A search from electronic databases PUBMED, MEDLINE, and CINAHL Plus retrieved 180 titles after removing duplicates, and a further 4 papers were identified by hand searching. Study of the abstracts identified 25 truly relevant articles, which were studied in full. Of these, 14 met our strict inclusion criteria. Most studies were cross-sectional; most were from Europe and have evaluated QoL in patients with oral lichen planus (OLP). The findings differ but, overall, do not provide evidence that patients with OPMDs have a poorer QoL compared with healthy patients. Several things may explain this apparently surprising conclusion. First, the quality of most articles was moderate or weak; second, most studies assessed QoL only in patients with OLP and cannot be generalized to all patients with OPMDs; last, direct comparisons between patients with OPMD and healthy controls were rarely included. The validity of the QoL instrument used for patients with OLP was frequently inadequate.