In acromegaly, clinical features are of the utmost importance, and biochemical confirmation is rarely difficult. However, some clinically manifest acromegalics have subtle abnormalities in GH secretion resulting in post-glucose GH nadir in the designated "normal" range with high IGF-I levels. Clinical decision may be based on the probability of the disease and elevated IGF-I levels. The TRH test or the frequent GH sampling test may help confirm acromegaly but on their own have no diagnostic advantage. A TRH-GH response is not specific to acromegaly, while frequent sampling is not practical. Other tests rarely add information beyond that obtained by usual investigations. Post-treatment assessment of the disease activity and definition of acromegaly cure, by measuring GH secretion, remain problematic. IGF-I levels seem to differentiate normality less clearly and discordance of GH and IGF-I results is frequent. Post-treatment probability for residual disease activity should include more clinical parameters such as insulin sensitivity, leptin and echocardiography. Furthermore, with efforts to achieve tight biochemical control of the disease it is foreseeable that a proportion of patients may be rendered GH deficient, requiring stimulatory testing. Acromegaly is a disfiguring and disabling illness, in which by definition, the disorder is caused by a pituitary GH-secreting adenoma resulting in high circulating levels of GH and IGF-I. The clinical features of acromegaly include those of GH and IGF-I on tissues and the effects of the pituitary tumor itself. There is no single cut-off value for GH with perfect discrimination between acromegaly and normality. The recommended post-glucose GH nadir value of 1 microg/l is now considered to be inappropriately high, and measurement of IGF-I levels although extremely valuable has its limitations. Furthermore, some acromegalics may have subtle abnormalities in GH secretion, resulting in post-glucose GH nadir in the designated "normal" range with elevated IGF-I levels.