Background: To make a diagnosis of growth hormone deficiency (GHD), individuals with normal GH levels must be distinguished from those who are deficient. This requires an understanding of how GH secretion and other related factors differs between these two groups. The presence of a normal insulin-like growth factor I (IGF-I) level does not necessarily preclude a diagnosis of GHD, whereas a low IGF-I level in a subject with three or four other hormone deficiencies and no conditions that would otherwise lower IGF-I might be sufficient to make the diagnosis. Provocative testing is a clinically relevant method of testing, but not all tests in use have comparable specificity and sensitivity. Conclusions: Insulin-induced hypoglycemia is the recommended test to diagnose GHD, but the arginine-GH-releasing hormone test achieves comparable separation between normal and hypopituitary subjects in most groups. Future studies using large surveillance databases may further expand our understanding of concepts underlying GHD and its diagnosis.