Gonadal steroids modulate the effects of GH, with oestrogens attenuating and androgens augmenting GH action. Whether these divergent effects influence the clinical manifestation, management and prognosis of acromegaly have not been carefully reviewed. This review examines whether there is a gender difference in epidemiology, presentation, quality of life (QoL), morbidity, treatments and mortality of acromegaly. Acromegaly is more common in women who present at an older age with longer diagnostic delay. At presentation, women have a higher GH relative to IGF-1 level than men. QoL is more adversely affected in women both before and after treatment. Prevalence of hypertension and diabetes are greater in women than in men with acromegaly. Treatment outcomes with SSAs are comparable between sexes, but women may require a higher dose of pegvisomant for equivalent response. Mortality in untreated acromegaly is more profoundly affected in women; however, improved treatments in recent decades have resulted in normalisation of standard mortality ratios in both sexes. We conclude that gender does matter in the management of acromegaly, with women presenting later in life, with greater diagnostic delay, higher prevalence of comorbidities and experiencing worse QoL.