Adult growth hormone deficiency (GHD) is associated with increased adiposity, reduced lean mass, adverse lipid profile, decreased bone density and impaired quality of life. Growth hormone (GH) replacement therapy provides significant metabolic, cardiovascular, musculoskeletal and psychological benefit. Traditional stimulation tests, such as the insulin tolerance and glucagon tests, are gold-standards for diagnosis, but the oral macimorelin test offers a safe, reliable and well-tolerated alternative. GH replacement should be titrated to achieve age-appropriate insulin-like growth factor 1 (IGF-1) levels. Monitoring should address potential side-effects, including glucose intolerance and fluid retention. Long-acting growth hormone (LAGH) formulations, such as somapacitan, lonapegsomatropin and somatrogon, now enable weekly administration, improving adherence while maintaining efficacy and safety comparable to daily therapy. Early evidence suggests enhanced patient satisfaction and similar metabolic outcomes. Ongoing longitudinal studies are essential to clarify long-term safety.