Background <p><i>Demodex</i> mites are among the most prevalent human parasites. While commonly found on healthy individuals, an overpopulation of this arachnid resident of human skin triggers demodicosis, a neglected yet widely prevalent disease with considerable skin and eye morbidity. Despite its health impact, demodicosis remains overshadowed by other common skin diseases. This neglect has significant consequences for individual and public health, which require a paradigm shift in our understanding and management of this ubiquitous ectoparasite.</p> Main abstract body <p>We reviewed the literature to re-evaluate the pathogenicity of the <i>Demodex</i> mite, paying particular attention to the primary risk factors—immune dysregulation, altered microbiota, and concurrent infections—that may contribute to pathogenicity. We discuss the challenges in combating neglect of demodicosis and provide updates on various impediments in achieving this goal. We explore the issues and research gaps in various domains such as those related to parasite biology, pathogenesis, diagnosis, treatment, prevention and control. We present potential solutions and outline future prospects for tackling this important disease. Finally, we hope to catalyze greater attention and investment for this neglected public health issue.</p> Conclusion <p>Raising awareness of <i>Demodex</i> and demodicosis and its major contribution to human diseases requires a multidisciplinary approach. Efforts to prioritize its place on the global health agenda, invest in research, improve diagnostic tools, and develop new treatment strategies will lead to improved public health outcomes and a higher quality of life for those affected.</p> Graphical abstract <p></p>