Context:Participation in lacrosse has dramatically increased since 2001. Changes in the game rules, sport equipment, and athlete characteristics have all contributed to the injury patterns in lacrosse over time.Objective:A summary of lacrosse-related musculoskeletal injuries.Data Sources:Medline, CINAHL, Scopus, and Web of Science were searched for articles relating to the epidemiology and mechanisms of lacrosse injuries in high school and collegiate lacrosse players.Study Selection:The search strategy used the following keywords: lacrosse, injury, musculoskeletal, high school, intercollegiate, knee, shoulder, fracture, ankle, foot, concussion, and surveillance. Studies were included if they reported injury risk, injury type, or injury mechanism in high school or collegiate lacrosse players.Study Design:Systematic review.Level of Evidence:Level 4.Data extraction:Injury type, frequency, and mechanism as well as population were extracted.Results:Thirteen cohort studies and an additional 15 case series and reports were included. For all lacrosse players, ankle, knee, and hand/wrist were key sites for acute injury. Among collegiate players, preseasonal play elicits more injuries than seasonal play. Female players incur more noncontact and overuse injuries than male players. Boys have 3 to 5 times the risk for sustaining a fracture compared with girls in competition and practice. Women experienced fewer concussions but more facial fractures than men. Injuries to the foot/ankle, head, face, and wrist/hand more often required surgery in girls than in boys.Conclusion:Male players incur more injuries than female players. However, because of the collisional nature of play, more shoulder, arm, and upper leg injuries occur in male players. Fractures to the head and hand occur relatively more frequently in female players. Injury risk can be modified with appropriate training regimens and by respecting the game rules.