At the crossover of specialties, the osmotic demyelination syndromes are under-diagnosed clinical entities. Even if the knowledge and the management of these entities have evolved in the latest years, many issues are still unsolved. Initially described as diseases affecting alcoholics and malnourished and considered affecting solely the pons, it is now known that osmotic demyelination can produce extrapontine lesions (extrapontine myelinolysis). Rapid correction of sodium in hyponatremic patients is pathogenically involved in the genesis of central pontine and extrapontine myelinolysis. The aim of this review is to focus on the main characteristics of the disease, which can represent a challenge for the clinicians in respect to its recognition and treatment.