Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder which is characterized by motor neuron (MN) dysfunction, progressive paralysis, and death. Although several therapeutic approaches have been used for treatment of ALS, little success has been resulted. Natural vectors such as mesenchymal stem cells (MSCs) can be a promising tool for overcoming to therapeutic problems. MSCs have multipotential characteristics such as the ability to differentiate into variety of cell types, easy access, immunomodulation, tissue repair, exertion of trophic factors, exosome secretion and efficient homing. In this review, we will discuss the characteristics of MSCs and their possible therapeutic mechanisms in ALS patients.