Therapeutic phlebotomy is the removal of red blood cells or serum iron from the blood. It is one of the preferred treatments for blood disorders. In ancient times this process was known as bloodletting. Generalized method included were venesection and arteriotomy and systemic methods included were cupping and by leeches. It stimulates bone marrow stem cells to generate new red blood cells (RBCs). Iron for hemoglobin synthesis is taken from the body thus reducing serum iron. Different indications of therapeutic phlebotomy include Polycythemia Vera, Hemochromatosis, Porphyria cutanea tarda, Sickle cell disease, Non-Alcoholic Fatty liver disease (NAFLD) with hyperferritinemia. Other methods available for reducing RBC and iron level include apheresis and administration of desferroxamine. Phlebotomy can cause rare adverse effects, such as thrombosis, mostly seen in patients with polycythemia Vera. Other adverse effects include Hematoma at phlebotomy site. Usually hematoma is mild but in severe cases can cause damage in nerves and surrounding tissue. Haemoconcentration, extravasation, Syncope and Fainting, petechiae, Excessive Bleeding, edema, arterial puncture, pain and anemia are some of the adverse effects caused by therapeutic phlebotomy. Unsafe phlebotomy can expose patients and health workers to various infections like Hepatitis B virus (HBV), Hepatitis C virus (HCV) and Human Immunodeficiency virus (HIV); syphilis and malaria. Different countries have approved allogenic use of blood units obtained from therapeutic phlebotomy. Mostly blood collected from patients with hemochromatosis is permitted. The article also discusses criteria for initiating therapeutic phlebotomy and various regimen followed in different diseases.