Inertial sensor systems are increasingly used in the assessment of persons with knee osteoarthritis (KOA) and total knee replacement (TKR). This systematic review aims to (1) investigate the application of inertial sensor systems and kinematics derived from these systems, and (2) assess if current assessment protocols consist of tasks which are, according to the International Classification of Functioning, Disability and Health (ICF) for KOA, relevant for persons with KOA and TKR. A search was conducted in six electronic databases (ACM, CINAHL, EMBASE, IEEE, PubMed, Web of Science) to include papers assessing the knee and one or more adjacent joints by means of inertial sensors in healthy persons or persons with KOA or TKR. Two reviewers checked the methodological quality. Twenty-three papers were included: 18 in healthy persons and five in persons with KOA or TKR. In healthy persons, 11 tasks were related to metrics of the ICF-function and ICF-activity level. In persons with KOA, only walking was assessed. Apart from walking, four additional tasks were related to the ICF-function and ICF-activity level in persons with TKR. In healthy persons, joints located proximally and distally to the knee were assessed, while in persons with KOA and TKR, only the knee and ankle were assessed. This is a shortcoming since hip and trunk motion potentially contain clinically relevant information, in terms of identifying (mal)adaptive compensatory movement strategies. Additionally, physically more demanding tasks should be evaluated as these might be superior in detecting compensatory movement strategies. Former considerations warrant attention in future research.