Limited knowledge of the neuromechanical response to use of an ankle foot orthosis-footwear combination (AFO-FC) has created a lack of consensus in understanding orthotic motion control as a therapeutic treatment. Lack of consensus may hinder the clinician’s ability to target the motion control needs of persons with movement impairment (e.g., peripheral nerve injury, stroke, etc.). Some evidence suggests a proportional relationship between joint motion and neuromuscular activity based on the notion that use of lower limb orthoses that constrain joint motion may invoke motor slacking and decreasing levels of muscle activity. Use of AFO-FCs likely alters the biomechanical and neuromuscular output as the central control system gradually forms new movement patterns. If there is proportional relationship between muscle activation and joint motion, then it could be examined by quantifying joint motion and subsequent neuromuscular output. Considering principles of neuromechanical adjustment, my general hypothesis examines whether orthotic control of lower limb motion alters neuromuscular output in proportion to the biomechanical output as a representation of the limb’s dynamics are updated by the neural control system. The rationale for this approach is that reference knowledge of the neuromechanical response is needed to inform clinicians about how a person responds to walking with motion controlling devices such as ankle foot orthoses combined with footwear. In the first line of research, I hypothesize that a newly developed AFO which maximizes leverage and stiffness will constrain the talocrural joint and alter joint kinematics and ground reaction force patterns. To answer the hypothesis, I sampled kinematics and kinetics of healthy subjects’ treadmill walking using an AFO-FC in a STOP condition and confirmed that the AFO substantially limited the range of talocrural plantarflexion and dorsiflexion motion to 3.7° and in a FREE condition maintained talocrural motion to 24.2° compared to 27.7° in a CONTROL (no AFO) condition. A follow up controlled static loading study sampled kinematics of matched healthy subjects limbs and cadaveric limbs in the AFO STOP and FREE conditions. Findings revealed healthy and cadaveric limbs in the AFO STOP condition substantially limited their limb segment motion similar to matched healthy subjects walking in the STOP condition and in the AFO FREE condition healthy and cadaveric limbs maintained similar limb segment motion to matched healthy subjects walking in the FREE condition. In a second line of research, I hypothesize that flexibility of a newly developed footwear system will allow normal walking kinetics due to the shape and flexibility of the footwear. To answer the hypothesis, I utilized a curved-flexible footwear system integrated with an AFO in a STOP condition and sampled kinematics and kinetics of healthy subjects during treadmill walking. Results revealed subjects elicited similar cadence, stance and swing duration and effective leg-ankle-foot roll over radius compared to walking in the curved-flexible footwear integrated with the AFO in a FREE condition and a CONTROL (no AFO) condition. To validate rollover dynamics of the curved-flexible footwear system, a follow up study of healthy subjects’ treadmill walking in newly developed flat-rigid footwear system integrated with the AFO in a STOP condition revealed interrupted leg-ankle-foot rollover compared to walking in curved-flexible footwear in STOP, FREE and CONTROL conditions. In a third line of research, I hypothesize that use of an AFO that limits talocrural motion in a STOP condition will proportionally reduce activation of Tibialis Anterior, Soleus, Medial and Lateral Gastrocnemii muscles compared to a FREE and CONTROL condition due to alterations in length dependent representation of the limb’s dynamics undergoing updates to the central control system that modify the pattern of motor output. To answer the question, the same subjects and AFO-footwear presented in the first two lines of research were used in a treadmill walking protocol in STOP, FREE, and CONTROL conditions. Findings revealed the same subjects and ipsilateral AFO-footwear system presented in Aim 1 exhibited an immediate yet moderate 30% decline in EMG activity of ipsilateral Soleus (SOL), Medial Gastrocnemius (MG) and Lateral Gastrocnemius (LG) muscles in the STOP condition compared to the CONTROL condition. The reduction in EMG activity in ipsilateral SOL, MG and LG muscles continued to gradually decline during 15 minutes of treadmill walking. On the contralateral leg, there was an immediate yet small increase of 1% to 14% in EMG activity in SOL, MG, LG muscles above baseline. After 10 minutes of walking, the EMG activity in contralateral SOL, MG and LG declined to a baseline level similar to the EMG activity in the contralateral CONTROL condition. These collective findings provide compelling evidence that the moderate 30% reduction in muscle activation exhibited by subjects as they experience substantial (85%) constraint of total talocrural motion in the AFO STOP condition is not proportionally equivalent. Further, the immediate decrease in muscle activation may be due to a reactive feedback mechanism whereas the continued decline may in part be explained by a feedforward mechanism. The clinical relevance of these findings suggests that short term use of orthotic constraint of talocrural motion in healthy subjects does not substantially reduce muscle activation. These preliminary findings could be used to inform the development of orthoses and footwear as therapeutic motion control treatments in the development of motor rehabilitation protocols.