Blood is an important fluid performing immense amount of physiological functions for the body. It is so precious that often termed as Red Gold. Red Blood Cells (RBCs) constitute a major portion, 40-45% total blood volume [1]. RBCs are responsible for oxygen transportation to tissues across the body and they are very ideal for this particular function [2]. According to a study conducted in 2011 approximately 50% patients that walk in to emergency department of hospitals need blood transfusion. This usually includes the patients ending up in Intensive Care Unit (ICU). Usually, purpose of blood transfusion is to improve the oxygen [3]. There are many significant studies stating that there is no efficient improvement in oxygen delivering capacity of patients even after transfusions. Some studies also associate blood transfusions with increased mortality and morbidity [4,5]. Allogeneic blood transfusions are very common medical interventions that can in some situations work like an elixir and save lives if blood that is being transfused go through a proper screening [6]. 1980’s was a time when human immunodeficiency virus was diagnosed very often to people; this became a matter of concern for public that blood that was being transfused was free of such infections [7]. Although blood transfusion itself is very regulated and standardized procedure but still it accompanied many risks [8]. Infectious (bacterial, viral) and non-infectious (transfusion associated lung injury) risks are most common. Immune response, agglutination reaction due to poor cross matching (ABO, Rh incompatibility) is more to name [9]. Hypersensitivity to transfused blood, nonhemolytic fibril transfusion reactions are also observed in many cases. Contamination of blood can be a result of processing and storage if donor was examined and found healthy at the time of blood donation [10]. Iron overload is also a drawback of allogeneic blood transfusion because on an average RBCs contain 250 mg of iron and repeated transfusions may result in iron build up [11]. Inadequacy of blood is a major issue now a day for developed countries. This compels the health regulating authorities to compromise the safety standards of donated blood [12]. Keeping all these risks and emergency use of blood in mind scientists are always in quest to find out safer replacements for blood e.g, artificial blood [13]. Many tries have been made but in vain. Scientists are not able to produce a liquid that mimics the blood function. In order to qualify as a blood replacement a liquid has to behave same as natural blood. It has to come into contact with every tissue in same way as natural blood do [14]. There has been a difficulty to develop blood replacements but scientists have evaluated certain solutions and compounds for their oxygen carrying ability and some of them gave promising results. So in general when we talk about blood substitutes we are actually referring to RBC substitutes (Oxygen therapeutics) to carry out tissue oxygenation. In this review we will discuss what current option we have. What are those compounds that qualify as blood substitutes and mimic oxygen carrying function of blood?