Knee injuries are common among sports and may represent significant lay off time. Among different potential knee injuries, the anterior cruciate ligament (ACL) injury is one of the most frequent and devastating sports-related conditions, leading to impaired function, long rehabilitation, and high reinjury risk. Given the substantial impact of ACL injuries and the considerable overlap among knee injury prevention programs, this chapter will center on prevention strategies targeting the ACL. Importantly, the core principles of ACL injury prevention can often be generalized to reduce the risk of other knee injuries. Over the past decades, prevention strategies have evolved from isolated quadriceps strengthening to comprehensive neuromuscular and biomechanical interventions. Effective programs integrate strength, plyometrics, agility, balance, proprioception, and technique feedback, targeting modifiable risk factors such as muscle strength, landing mechanics, fatigue, footwear, and playing surface. Non-modifiable factors, including female sex, adolescence, anatomic variations, and prior injury, highlight the importance of individualized risk assessment. Muscle conditioning, particularly of hamstrings and medial quadriceps, plays a central role in unloading the ACL and enhancing stability, while proprioceptive and neuromuscular training reduce noncontact injury rates significantly. Although prophylactic and functional knee bracing remain controversial, their role in perceived stability and sport-specific use continues to be explored. Emerging evidence highlights neurocognitive function and decision-making as critical determinants of injury risk, encouraging incorporation of unplanned, reactive drills into prevention. Biomechanical evaluation, from advanced 3D motion capture to accessible wearable sensors, supports large-scale screening and feedback. Finally, structured secondary prevention and multidisciplinary rehabilitation, exemplified by the Aspetar method, have demonstrated reduced reinjury rates and safer return to sport, underscoring the importance of individualized, evidence-based strategies.