There is an increasing trend in youth female participation in sports worldwide. This situation comes with increased injury incidence, especially in female athletes. Disparities in anatomical, hormonal, and neuromuscular factors between males and females contribute to an elevated risk of anterior cruciate ligament (ACL) injuries in female athletes. Research has shown that females are more prone to ACL injuries due to differences in anatomy, hormones, and neuromuscular control compared to their male counterparts. Understanding the basic differences is crucial in effectively addressing the rising injury rate among female athletes. Prevention strategies tailored to the biomechanics and strength training needs of female athletes have been developed and have shown effectiveness in reducing injuries. Current prevention strategies primarily focus on neuromuscular training and plyometric exercises and are evolving rapidly. While a perfect program that completely eliminates the risk of ACL injuries in female athletes has not been achieved, ongoing efforts continue to enhance injury prevention strategies. Continued research and valuable feedback from implementing prevention programs in the field are essential to enhancing the effectiveness of current strategies. This chapter examines the characteristics and prevention strategies for ACL injuries in females. It also aims to enlighten physicians about the basic science behind female ACL injuries, as well as the development and effectiveness of injury prevention programs.