Running in a fatigued state has been proposed as one of the primary factors relating to overuse injuries associated with running. Patellofemoral pain (PFP) syndrome has long been the most common overuse injury that runners sustain, yet the etiology of PFP is not clearly understood. The overall goal of this work was to examine lower extremity kinematics and joint coupling over the course of a prolonged run in runners with and without PFP. In aim one of this work, lower extremity kinematics and joint coupling were analyzed in 20 uninjured runners over a prolonged run. Running with exertion was associated with small increases in kinematics, and altered continuous relative phase (CRP) coupling patterns during the first half of stance. In the second aim, the lower extremity kinematics of 20 runners with PFP were compared to 20 uninjured runners over a prolonged run. The PFP group displayed less overall motion, suggesting a strategy of stiffening the leg in response to pain. Three distinct PFP subgroups emerged, with each subgroup demonstrating unique kinematic patterns, suggesting that a number of different kinematic mechanisms for PFP may exist. In aim three, lower extremity joint coupling of 20 runners with PFP were compared to 20 uninjured runners over a prolonged run. The PFP group demonstrated prolonged eversion and an earlier peak knee internal rotation, which disrupted the normal coupling throughout the leg. At the end of the run, CRP coupling in the PFP group resembled the uninjured group at the beginning, suggesting a compensatory strategy in response to pain. In aim four, hip strength, and its relationship to hip angles when running, was compared between 20 runners with PFP and 20 uninjured runners. The PFP group displayed weaker hip muscles, which related to increased hip adduction when running, suggesting a minimum level of hip strength is needed to maintain femoral alignment when running. In summary, runners with PFP exhibit abnormal kinematics and joint coupling over a prolonged run, which may be related to weaker hip muscles. This work demonstrates that PFP is likely a multifactorial syndrome, and prevention and treatment strategies should be tailored accordingly.