Motor and cognitive impairments are commonly examined independently of each other, but the understanding of task-dependent interaction between cognitive and motor systems, each with distinct neuroanatomic substrates, has highlighted an interaction between them. There is increasing evidence on the impact of the motor and cognitive interaction in neurodegenerative disorders and other clinical populations such as dementia, stroke, Parkinson's disease, and multiple sclerosis. Therefore, great effort has been dedicated to developing rehabilitative strategies targeting motor-cognitive interactions to improve conditions in these diseases. This Special Issue of Brain Sciences covers the latest advances in the understanding of key mechanisms of motor-cognitive interactions and related innovative treatments.