Objective: The aim of this review is to provide a synthesis of studies exploring biased interpretation of ambiguous information in individuals with chronic pain, and to meta-analyze the results of studies comparing individuals with chronic pain to pain-free controls. Method: Studies were identified via a search of Medline, PsycINFO, Web of Science, CINAHL, and Cochrane Library databases. Search terms were bias*, interpretation, and ambiguous, intersected with the term pain. Results: Seven eligible studies (featuring 445 individuals with chronic pain, and 407 pain-free controls including 170 health professionals) using 4 different paradigms (word stem completion task, homographic response task, homophone task, incidental learning task) were identified and included. All 7 studies provided evidence of significantly more frequent pain-related/illness-related interpretations of ambiguous words (which also have possible neutral interpretations) or images (morphed painful and happy facial expressions) in individuals with chronic pain relative to healthy controls. This was confirmed by a significant between-groups difference in a meta-analysis of available data from 4 studies (Hedges’ adjusted g effect size = 0.67). Conclusions: Individuals with chronic pain demonstrate biased interpretation of ambiguous information favoring pain-related/illness-related interpretations. A number of important methodological limitations are apparent however, including potential sources of bias in the classification of participant responses in some paradigms. Further research adopting more rigorous methodology is therefore required. Another area for future research is investigation into how different forms of cognitive bias (i.e., attentional, interpretation, and memory biases) interact with one another in chronic pain patients.