It is generally known that growth hormone (GH)-deficient patients experience emotional instability, reduced energy, sleep disturbances, and problems with (sexual) relationships. GH and insulin-like growth factor-1 (IGF-I) may affect mood parameters by their actions at binding sites in specific brain areas and/or by their effects on dopamine turnover in the brain. Indeed, there is substantial evidence that somatropin (growth hormone) treatment improves the quality of life (QOL) of GH-deficient patients. However, the variety of instruments used makes it questionable whether QOL in particular is affected by somatropin therapy. The measurement of QOL is subject to methodologic difficulties and is frequently not properly distinguished from health status and well-being. QOL ratings are characterized by an emphasis on mental health and health status by an emphasis on physical function, while well-being is concerned with depression, anxiety, and energy levels. Examples of instruments used to measure QOL, health status, and well-being in GH-deficient patients are the Quality of Life-Assessment of Growth Hormone Deficiency in Adults, the Short-Form Health Survey, and the Psychological General Well-Being Schedule, respectively. One additional problem in establishing the effects of somatropin treatment on QOL is that the QOL effects of somatropin treatment may be different for patients with isolated GH deficiency (GHD) and those with multiple pituitary hormone deficiencies. Previously, in order to answer the question of whether somatropin therapy improves mood status in GH-deficient patients, we conducted a meta-analysis comparing somatropin treatment effects relative to baseline and placebo. At 3, 6, and 12 months of somatropin replacement the mood status of GH-deficient patients improved with decreasing effect sizes over time (d = 0.81, 0.55, and 0.29, respectively) from baseline. However, the median somatropin treatment period of 6 months did not improve mood status more than placebo. In a second analysis we classified the questionnaires into those on QOL, those on health status, and those on well-being, respectively, and analyzed the separate effects of pooled treatment durations of about 9 months. Somatropin replacement improved QOL with a small effect size (d = 0.18), well-being with a medium effect size (d = 0.47), and health status with a small effect size (d = 0.26). Although the separate effects of somatropin on QOL, health status, and well-being could not be compared to placebo, we concluded that somatropin treatment most likely plays a role in improving the well-being of patients with GHD. This conclusion is based on correlations that have been found between IGF-I levels and parameters of well-being, such as anxiety and depression.