On behalf of the American Society for Parenteral and Enteral Nutrition (ASPEN), a systematic review was conducted to evaluate the best available evidence regarding the validity of relevant body composition methods (eg, dual energy X-ray absorptiometry [DXA], ultrasound [US], and bioelectrical impedance analysis [BIA]) in clinical populations. The guidelines targeted adults >18 years of age with a potentially inflammatory condition or pathological end point associated with a specific disease or clinical condition. In total, 7375 studies were retrieved, and 15 DXA, 7 US, and 23 BIA studies provided applicable data. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses was used to assess the diagnostic accuracy of the test method against a "gold standard" reference. The Grading of Recommendations, Assessment, Development and Evaluation criteria were used to separate the evaluation of the body of evidence from the recommendations. Based on a limited number of studies and expert opinion, DXA is recommended for the assessment of fat mass in patients with a variety of disease states; however, the validity of DXA for lean mass assessment in any clinical population remains unknown. No recommendations can be made at this time to support the use of US or BIA in the clinical setting, as data to support its validity in any specific patient population are limited in scope or by the proprietary nature of manufacture-specific BIA regression models to procure body composition data, respectively. Directions for future research are provided. These clinical guidelines were approved by the ASPEN Board of Directors.