Hypopituitarism is a disease complex characterised by varying pituitary hormonal deficiencies. The causes and manifestations of hypopituitarism are diverse, the most common being the presence of or treatment of a pituitary adenoma. Pressure effects from the tumour itself on normal pituitary tissue, together with the effects of surgical resection, results in variable degrees of hypopituitarism. The latter precipitates end-organ failure leading to a variety of symptoms and signs, which are often nonspecific and vague. The broad aims of managing patients with hypopituitarism are to provide amelioration of the symptomatology associated with the condition, to avoid potentially acute life-threatening complications and to protect against long-term sequelae that may include osteoporosis and cardiovascular disease. This is achieved through lifelong therapeutic replacement of target hormonal deficiencies, such as corticosteroids or sex hormones, or replacement of the pituitary hormones themselves (i.e., growth hormone and vasopressin). Although the general principle of replacing missing hormones seems straightforward, in reality, existing hormonal therapeutic regimes often result in unphysiological replacement. Furthermore, there may be problems associated with their administration and routine monitoring. There is now little doubt that the hypopituitary state is associated with increased cardiovascular mortality. However, the precise underlying mechanisms responsible have not been fully elucidated, but probably include untreated growth hormone deficiency and/or unphysiological replacement of other target hormones. An effective strategy of tailoring hormonal replacement regimes to individual needs remains a challenge but is imperative if the increased morbidity and mortality associated with hypopituitarism is to be addressed.