Methods of treating, preventing and/or managing central nervous system disorders, such as Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig's Disease) and related syndromes are disclosed. Specific methods encompass the administration of thalidomide, or a pharmaceutically acceptable salt, solvate, hydrate, or stereoisomer thereof, alone or in combination with a second active ingredient. Pharmaceutical compositions, single unit dosage forms, and kits suitable for use in methods of the invention are also disclosed.