Orthopaedic problems can be caused or accentuated by both normal and abnormal gait characteristics. Traditionally, footwear modifications and orthotic interventions have been limited to internal and external wedges and other assorted orthotics. This thesis will discuss various methods to measure biomechanical responses of human subjects in response to changes in footwear design. Chapter 1 provides an overview of what is currently known regarding interventions in relation to providing medial compartment knee osteoarthritis relief as well as limiting excessive rear-foot motion. Chapter 2 discusses a method for measuring the center of pressure in multiple steps using an insole pressure measurement system and evaluating the effect that varying midsole stiffness has on the center of pressure. Chapter 3 presents a dynamic segmental model for knee adduction moment measurements and how a full lateral stiffened shoe and five other prototype shoes with varying midsole stiffness change that moment in healthy subjects. Chapter 4 presents a method for measuring rear-foot motion and evaluates a new footwear technology designed to reduce excessive rear-foot motion. Chapter 5 is a summation of the thesis and recommendations for future studies. The information in this thesis could be helpful in providing strategies for changing location and stiffness values of footwear midsoles to elicit positive biomechanical responses in human subjects during gait.