Human monkeypox is a zoonotic Orthopoxvirus resembling smallpox in clinical course, making it difficult to distinguish it from smallpox and varicella. Laboratory diagnostics are critical components of illness identification and surveillance, and novel tests are required for more precise and quick diagnosis. The majority of human infections occur in Central Africa, where monitoring in remote regions with little infrastructure is challenging but may be performed using evidence-based methods and teaching materials that educate public health personnel on the fundamental principles of this infection. New medications and vaccinations showed promising results for the treatment and prevention of the disease, but more studies are required to show their efficacy in the actual endemic settings. Thus, more studies are needed on the virus's epidemiology, ecology, and biology in endemic locations to better understand and prevent human infections. This review discussed the etiology, epidemiology, and clinical course of the monkeypox and indicated diagnostic and treatment approaches for this disease.