<p>Growth hormone deficiency (GHD) in childhood and adolescence requires long-term therapy with recombinant human growth hormone (rhGH). Although daily injections are highly effective, they impose a considerable treatment burden that often leads to suboptimal adherence and compromised growth outcomes. Reported non-adherence rates vary widely, largely due to heterogeneous definitions and assessment methods. Adherence is influenced by multiple factors, including device usability, psychosocial context, family engagement, and the level of support from health care professionals. Although Long-Acting Growth Hormone (LAGH) preparations, administered once weekly, have demonstrated efficacy and safety comparable to daily rhGH in clinical trials, adherence in these settings may be overestimated. The key question now is whether LAGH can truly enhance treatment adherence in real-world settings. This narrative review summarizes the very limited data currently available on adherence to LAGH in both treatment-naïve patients and those switching from daily rhGH, highlighting methodological heterogeneity and the absence of robust long-term outcomes. Rather than providing definitive conclusions, our aim is to map existing evidence, identify critical gaps, and outline priorities for future real-world and longitudinal studies evaluating adherence, persistence, and clinical consequences of poor adherence in LAGH users.</p>