OBJECTIVES: To review the cost-effectiveness literature evaluating positron emission tomography (PET) imaging. METHODS: We systematically searched the PubMed database and the Tufts Medical Center Cost-Effectiveness Analysis Registry to identify studies evaluating the economics of PET imaging.  We categorized each study with respect to indication, i.e., cardiology, neurology, oncology, and other.  We extracted data pertaining to:  the date of publication; the region in which the study was set; methods employed; the inclusion of active comparators; and study endpoints.  Data was extracted from each study using a predefined data extraction form.   RESULTS: Seventy studies met our inclusion criteria and were included in our dataset.  Many of these analyses’ have concluded that PET is cost-effective; 38% of the cost-effectiveness analyses’ findings indicate ICERs less than $50,000 (2012 USD).  Growth in the cost-effectiveness literature for PET parallels growth of the cost-effectiveness literature more broadly with 35% of studies published since 2009.  Across all years, a smaller proportion of studies examining PET emanated from the US than did cost-effectiveness analyses generally (29% vs. 42%).  The majority of studies examined PET for oncological indications (n=58; 83%).  The most common analytical method employed was cost-effectiveness analysis, although two cost-minimization studies were also identified.  Studies typically compared PET to either x-ray computed tomographic imaging or usual care.  Diagnostic accuracy was the most common unit of effectiveness reported. CONCLUSIONS: There is substantial literature evaluating the cost-effectiveness of PET across a range of indications.  Most studies have examined diagnostic accuracy and not considered endpoints, such as how PET imaging influences clinical decision making or changes patient outcomes.