Active acromegaly can be treated effectively by transsphenoidal surgery, radiotherapy and medical treatment in the form of somatostatin analogs and growth hormone receptor antagonists. Many patients will require a combination of treatment modalities to normalize growth hormone excess and associated increased mortality, and to improve comorbidity. Following postoperative radiotherapy, growth hormone and insulin-like growth factor-I levels gradually decrease and normalization of growth hormone and insulin-like growth factor-I is achieved in 50% of patients after 5 years and 75% after 10 years. Disadvantages of radiotherapy include the long interval until hormone levels have sufficiently decreased and the high incidence of radiation-induced hypopituitarism. Radiotherapy was associated with increased mortality in some but not other studies. Limitations in the design and confounding factors, such as years spent with active disease and changing treatment strategies, make it impossible to draw conclusions on this topic. Gamma knife radiosurgery may combine faster decline of growth hormone excess with a lower incidence of hypopituitarism in eligible cases, but long-term results of this radiation technique are lacking. At present, patients will preferentially be treated by primary surgery and/or somatostatin analog treatment, followed, if necessary, by growth hormone receptor antagonist treatment, while radiotherapy is reserved for selected cases only. The indications for radiotherapy and radiosurgery need to be revisited in the near future, when longer follow-up results for medical treatment and radiosurgery have become available. This review summarizes the recent literature on efficacy and side effects of radiotherapy and radiosurgery in acromegaly and discusses the place of radiation treatment in the treatment algorithm of acromegaly.