The current increase of life expectancy is associated with the presence of endocrine diseases in the elderly. The management of hypopituitarism in this group of patients is a challenging task. A correct diagnosis, which represents an essential requisite for an appropriate medical treatment, can be difficult because of the physiological changes occurring in pituitary function with aging, which may lead to challenges in the interpretation of laboratory results. Furthermore, the treatment requires several careful considerations: the need to restore the hormonal physiology with replacement therapies must be balanced with the need to avoid the risks of the over-replacement, especially in the presence of concomitant cardiovascular and metabolic disease. Interactions with other drugs able to modify the absorption and/or the metabolism of hormonal replacement therapies should be considered, in particular for the treatment of hypoadrenalism and hypothyroidism. The most important challenges stem from the lack of specific studies focused on the management of hypopituitarism in older people.