The use of inertial measurement units (IMUs) has gained popularity for the estimation of lower limb kinematics. However, implementations in clinical practice are still lacking. The aim of this review is twofold-to evaluate the methodological requirements for IMU-based joint kinematic estimation to be applicable in a clinical setting, and to suggest future research directions. Studies within the PubMed, Web Of Science and EMBASE databases were screened for eligibility, based on the following inclusion criteria: (1) studies must include a methodological description of how kinematic variables were obtained for the lower limb, (2) kinematic data must have been acquired by means of IMUs, (3) studies must have validated the implemented method against a golden standard reference system. Information on study characteristics, signal processing characteristics and study results was assessed and discussed. This review shows that methods for lower limb joint kinematics are inherently application dependent. Sensor restrictions are generally compensated with biomechanically inspired assumptions and prior information. Awareness of the possible adaptations in the IMU-based kinematic estimates by incorporating such prior information and assumptions is necessary, before drawing clinical decisions. Future research should focus on alternative validation methods, subject-specific IMU-based biomechanical joint models and disturbed movement patterns in real-world settings.