The locked-in syndrome (LIS) is a severe condition originated by a ventral pons lesion causing quadriplegia and anarthria but with a preserved consciousness. LIS seems to be a well defined clinical picture, although different problems still persist, such as the diagnosis as it is usually mistaken for akinetic mutism and a vegetative state; the unclear prognosis, because of the patient's psychological state and the lack of information and data concerning the different types of available treatment and the need for results. Rehabilitation is a challenge for physicians, new methods and techniques of specialized treatments for these patients are opening a new future that will allow us to abandon the initial pessimism. A more efficient rehabilitation of these patients depends on the intensity of the rehabilitation, the multidisciplinary approach, and duration of the treatment.