Over the last decade, different guidelines have been published for the diagnosis, treatment and monitoring of adult growth hormone deficiency (AGHD). Themes and recommendations common to the guidelines offer a pragmatic approach to the management of AGHD. Nevertheless, there is a need for more research in some key areas in which recommendations in the guidelines are supported by moderate evidence, at best. Recent meta-analysis and long-term follow-up studies have contributed with valuable information on the efficacy and safety of GH therapy in adults. This review brings a historical perspective of the AGHD, with an emphasis on the following aspects: (I) who are the appropriate candidates for GH therapy in adult life? (II) how to make the diagnosis (III) the impact of GH therapy; (IV) which therapeutic approach should be used? (V) how to follow and monitor the patients; and (VI) special aspects on mortality and longevity related to the GH-IGF-1 axis.