Over 650,000 total knee arthroplasties (TKAs) are performed annually in the United States to alleviate knee osteoarthritis (OA) Yrelated pain and disability (1). This number is expected to increase to 3.48 million per year by 2030 (12). Although TKA reliably reduces pain and improves self-reported function, quadriceps strength fails to recover to levels of healthy, age-matched adults even years after surgery. Quadriceps muscle weakness has profound functional consequences and is associated with decreased gait speed (4), balance (17), stair climbing (14), and chair rise (25) ability, as well as increased risk for falls (16). Therefore, it is not surprising that physical function, like quadriceps weakness, remains impaired in more than 50% of patients 1 yr after TKA (19). As such, attenuating quadriceps strength deficits is imperative to limiting disability later in life. Long-term deficits in quadriceps strength may stem from preoperative weakness and postoperative strength loss. Individuals with tibiofemoral OA demonstrate quadriceps weakness compared with individuals without radiographic evidence of the disease (20). Postoperatively, patients experience a 60% decrease in quadriceps strength 3Y4 wk after surgery from preoperative levels (15). Both preoperative and postoperative strength loss may be attributable to impaired quadriceps activation. Muscle atrophy may explain further postoperative quadriceps weakness (15); however, central activation deficits (CAD) reportedly account for twice the strength loss as muscle atrophy early after surgery (15). Quadriceps CAD are prevalent in individuals with knee OA, although CAD are magnified after TKA (15), resulting in more severe muscle weakness than before surgery. Although recent evidence suggests that quadriceps CAD largely resolve within the first postoperative year (21), these early deficits and related muscle weakness may contribute substantially to the long-term muscle weakness documented in these patients. Specifically, the presence of quadriceps CAD may contribute to early muscle atrophy and also hinder the ability to restore muscle mass, further impairing quadriceps strength long-term. As such, we contend that reducing CAD early after TKA is imperative to countering quadriceps weakness and more effectively restoring functional performance. In this article, we provide several strategies for attenuating CAD after TKA as well as directions for future research to further understand and treat postoperative CAD.