Purpose: This systematic review of literature analyzed accelerometer use to measure physical activity (PA) in individuals 21 years and younger with Down syndrome (DS). Summary of Key Points: Comprehensive search strategy conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eight articles met inclusion criteria. Six studies reported children with DS are not meeting PA guidelines; 4 studies found intensity levels decline with age. Three studies reported children with DS engage in significantly less vigorous PA than control groups. Determination of intensity levels varied, limiting additional comparisons. Conclusions: Children with DS engage in less PA than peers developing typically and are not meeting PA guidelines across age groups, increasing risk for numerous health conditions secondary to decreased activity. Recommendations for Clinical Practice: Promotion of more appropriate levels of PA and elimination of barriers to participation in PA are important for individuals with DS.