This chapter explores the biomechanics of the foot and ankle across important adult and childhood rheumatic diseases including rheumatoid arthritis, the seronegative spondylarthropathies, connective tissue disease, and juvenile idiopathic arthritis. The chapter draws on key literature and our own insights and experiences from clinical practice and research. Key biomechanical concepts are illustrated through selected patient case studies. In this clinical field, foot and ankle biomechanics is dominated by three-dimensional gait analysis research that describes pathological gait as a consequence of persistent primary disease mechanisms involving the joint, entheses, and tendons of the foot and ankle. We provide extensive descriptions of changes to spatio-temporal gait patterns as a product of impairment-driven compensation and destruction of foot and ankle joints. We explore how joint kinematics and kinetics, electromyographic muscle function, and plantar pressure distribution are disrupted across the life course of each rheumatic disease. We relate these observed changes to joint and soft tissue pathology, for example synovitis and enthesitis, that disrupt normal foot structure and function. We also attempt to explore the relationship between the patients’ lived experience in terms of impairments such as joint pain, stiffness and deformity, and ultimately progressive and irreversible disability, with biomechanical changes as detected and quantified via gait analysis. The chapter concludes with suggestions for future research that may lead to translational biomechanical breakthroughs to advance diagnoses and improve patient outcomes.