Once-weekly long-acting growth hormone (LAGH) preparations have demonstrated noninferiority compared to daily recombinant human growth hormone in terms of increased growth velocity and improved body composition with comparable short-term safety profiles in children with growth hormone deficiency (CGHD) and adults with growth hormone deficiency (AGHD). Currently, three LAGH preparations are approved for treatment of CGHD and one for AGHD. These agents may improve patient adherence, quality of life, and clinical outcomes. Clinicians will need to identify the best candidates for LAGH therapy and understand how to start, monitor, and adjust therapy. Long-term surveillance studies are required to demonstrate adherence, efficacy, cost-effectiveness, and safety.