Mechanical loading to the knee joint results in a differential response based on the local capacity of the tissues (ligament, tendon, meniscus, cartilage, and bone) and how those tissues subsequently adapt to that load at the molecular and cellular level. Participation in cutting, pivoting, and jumping sports predisposes the knee to the risk of injury. In this narrative review, we describe different mechanisms of loading that can result in excessive loads to the knee, leading to ligamentous, musculotendinous, meniscal, and chondral injuries or maladaptations. Following injury (or surgery) to structures around the knee, the primary goal of rehabilitation is to maximize the patient’s response to exercise at the current level of function, while minimizing the risk of re-injury to the healing tissue. Clinicians should have a clear understanding of the specific injured tissue(s), and rehabilitation should be driven by knowledge of tissue-healing constraints, knee complex and lower extremity biomechanics, neuromuscular physiology, task-specific activities involving weight-bearing and non-weight-bearing conditions, and training principles. We provide a practical application for prescribing loading progressions of exercises, functional activities, and mobility tasks based on their mechanical load profile to knee-specific structures during the rehabilitation process. Various loading interventions can be used by clinicians to produce physical stress to address body function, physical impairments, activity limitations, and participation restrictions. By modifying the mechanical load elements, clinicians can alter the tissue adaptations, facilitate motor learning, and resolve corresponding physical impairments. Providing different loads that create variable tensile, compressive, and shear deformation on the tissue through mechanotransduction and specificity can promote the appropriate stress adaptations to increase tissue capacity and injury tolerance. Tools for monitoring rehabilitation training loads to the knee are proposed to assess the reactivity of the knee joint to mechanical loading to monitor excessive mechanical loads and facilitate optimal rehabilitation.