The aim of this Task Force was to review the use of dual-energy X-ray absorptiometry (DXA) in children and adolescents with underlying chronic diseases that pose risk factors for compromised bone health, such as inflammation, glucocorticoid therapy, or decreased mobility. The Task Force systematically analyzed more than 270 studies, with an emphasis on those published in the interval since the original 2007 Position Statements. Important developments over this period included prospective cohort studies demonstrating that DXA measures of areal bone mineral density (aBMD) predicted incident fractures and the development of robust reference data and strategies to adjust for bone size in children with growth impairment. In this report, we summarize the current literature on the relationship between DXA-based aBMD and both fracture (vertebral and non-vertebral) outcomes and non-fracture risk factors (e.g., disease characteristics, ambulatory status, and glucocorticoid exposure) in children with chronic illnesses. Most publications described the aBMD profile of children with underlying diseases, as well as the cross-sectional or longitudinal relationship between aBMD and clinically relevant non-fracture outcomes. Studies that addressed the relationship between aBMD and prevalent or incident fractures in children with chronic illnesses are now emerging. In view of these updated data, this report provides guidelines for the use of DXA-based aBMD in this setting. The initial recommendation that DXA is part of a comprehensive skeletal healthy assessment in patients with increased risk of fracture is unchanged. Although the prior guidelines recommended DXA assessment in children with chronic diseases at the time of clinical presentation with ongoing monitoring, this revised Position Statement focuses on the performance of DXA when the patient may benefit from interventions to decrease their elevated risk of a clinically significant fracture and when the DXA results will influence that management.