Management of myasthenic crisis (MC) requires admission of the patient into a neurological intensive care unit and timely institution of an efficient and safe treatment. Despite the growing clinical experience with disease modifying immunotherapy there is no clinical consensus regarding the use of plasma exchange or high dose immunoglobulin treatment in an ICU setting. The choice of treatment modalities seem to rely mostly on institutional preferences primarily due to a lack of well-designed clinical trials comparing currently available therapeutic options. In our experience and based on a review of recent literature we advocate the use of plasma exchange (PE) as a primary modality in the acute care setting, supported by other immunomodulatory medications such as corticosteroids. Pharmacological management cannot substitute for adequate intensive care management of the respiratory and bulbar insufficiency associated with MC. Every effort should be done to prevent myasthenic exacerbation/crisis and to develop a maintenance management that leads to effective prevention.