Purpose of review After extensive research and many years of waiting, long-acting growth hormone (LAGH) formulations have finally become a reality in clinical practice and emerge as a potential solution to address the challenges of daily injections of recombinant human GH (rhGH). In this review, we present a brief history of the development of LAGH and provide a critical analysis of the existing literature on the five LAGH available and approved to date for treatment in children. Recent findings In clinical trials, LAGH therapy has shown noninferiority compared with daily rhGH therapy in promoting linear growth in children with GH deficiency, with similar rates of adverse events. Summary In the real world, many questions still need to be answered, such as whether a specific group of patients will benefit most from the weekly injection, whether compliance will be better compared with daily rhGH, whether long-term efficacy, monitoring and safety profile will be the same for the different LAGH compounds, and whether the cost-effectiveness will justify their use in different settings.