Growth hormone (GH) therapy is widely used for the treatment of GH deficiency, as it improves body composition, bone density, and cholesterol levels and may decrease death. Although it is referred by some as the “sweet syringe of youth,” its role in the healthy elderly is still controversial. GH therapy can lead to adverse effects that might progress to serious morbidity, such as carpal tunnel syndrome, fluid retention with peripheral edema, arthralgias, swelling of joints, gynecomastia, and glucose intolerance. Furthermore, several studies have also hypothesized a potential role for GH in malignancy. This review evaluates the role of GH therapy on the risk of malignancy. Mouse models clearly support a role for GH in cancer. In humans, elevated levels of GH are associated with an increased risk of breast, gastric, large bowel, lung, and prostate cancer. In patients treated with GH replacement therapy enrolled in KIMS (Pfizer International Metabolic Database), no relation with increased incidence of neoplasms was found. Also, other studies in GH-deficient patients with long-term GH therapy showed no increased risk of recurrence of primary tumors. However, the effect of GH therapy on the development of second cancers is still controversial. Although theoretically GH therapy might increase the risk of cancer, clinical studies so far have not supported this hypothesis, and it seems that long-term GH therapy is safe in hypopituitary patients with GH deficiency. However, long-term monitoring is advised in terms of underlying neoplasia, as well as other adverse effects of GH therapy.