Background: The Nile River and the liver disease schistosomiasis share a dramatic story that unites them. Egypt is the Nile's gift to the world, as it gives it goodness and growth. On the other hand, it brings to Egypt the oldest disease in its history, schistosomiasis Aim: We aimed to review the 5 thousand years history of Schistosoma in Egypt, its relation to the Nile River, and its effect on Egyptian life and health, as well as to shed light on the efforts of the Egyptian Ministry of Health to control it in the last century, current situation, and perspectives. Results: Schistosoma in ancient Egyptian mummies proved the disease was present over 5000 years ago. Theodor Bilharz, a German professor after whom the disease is named, discovered the Schistosoma in1850. In 1937, studies found that schistosomiasis affected more than 60% of the population in rural areas. In 1926, the government initiated mass treatment and snail control programs and campaigns to combat schistosomiasis and it continued for the past 100 years, leading to a decline in the prevalence of schistosomiasis from 60% in 1937 to approximately 0.2% in 2016. Recent studies have revealed an increase in incidence in certain areas of Egypt, which raises serious concerns. Conclusion: The story of the schistosomiasis in Egypt extends more than 5000 years and despite the efforts of the state for more than a hundred year; this requires the continuation of research, treatment and control campaigns especially in the most endemic and widespread places in Egypt.