Following anterior cruciate ligament (ACL) injury, quadriceps muscle atrophy persists despite rehabilitation, leading to loss of lower limb strength, osteoarthritis, poor knee joint health and reduced quality of life. However, the molecular mechanisms responsible for these deficits in hypertrophic adaptations within the quadriceps muscle following ACL injury and reconstruction are poorly understood. While resistance exercise training stimulates skeletal muscle hypertrophy, attenuation of these hypertrophic pathways can hinder rehabilitation following ACL injury and reconstruction, and ultimately lead to skeletal muscle atrophy that persists beyond ACL reconstruction, similar to disuse atrophy. Numerous studies have documented beneficial roles of nutritional support, including nutritional supplementation, in maintaining and/or increasing muscle mass. There are three main mechanisms by which nutritional supplementation may attenuate muscle atrophy and promote hypertrophy: (1) by directly affecting muscle protein synthetic machinery; (2) indirectly increasing an individual's ability to work harder; and/or (3) directly affecting satellite cell proliferation and differentiation. We propose that nutritional support may enhance rehabilitative responses to exercise training and positively impact molecular machinery underlying muscle hypertrophy. As one of the fastest growing knee injuries worldwide, a better understanding of the potential mechanisms involved in quadriceps muscle deficits following ACL injury and reconstruction, and potential benefits of nutritional support, are required to help restore quadriceps muscle mass and/or strength. This review discusses our current understanding of the molecular mechanisms involved in muscle hypertrophy and disuse atrophy, and how nutritional supplements may leverage these pathways to maximise recovery from ACL injury and reconstruction.