Muscle strains of the quadriceps group are common, and occur mostly in the rectus femoris. Strains occur most often when muscles are suddenly activated while on stretch, during either eccentric or concentric contraction. We report 2 cases of vastus lateralis strain that occurred in association with clinical histories of patellofemoral pain syndrome. Symptoms described included anterior knee pain associated with prolonged sitting with the knee flexed, and anterior knee pain associated with running, stair climbing, and jumping. These symptoms preceded the acute strain by at least 1 year. These cases emphasize a clinician's need to understand knee biomechanics, and the need to consider the entire kinetic chain when managing pain and injury in an extremity.