Certain physical and physiological changes occur in the atmospheric levels where flight and space activities take place. Air pressure decreases with increasing altitude and the partial pres­sure of O2 decreases in parallel with the atmospheric pressure drop and creates hypoxia in the flight crew and in the passen­gers. In case of acute hypobaric hypoxia, blood is redistributed to the brain and the heart, whereas blood supply to internal organs, such as kidney and skin is reduced. Peripheral cyanosis can be observed on the fingertips and the lips during hypoxia-induced blood redistribution. Tachycardia develops, but the stroke volume does not change. The coronary blood flow increases in parallel with the rise of cardiac output; however, the presence of severe hypoxia leads to myocardial depression. Coronary reflex vasoconstriction is followed by cardiac arrest. Another important pathology caused by low pressure is decompression sickness. In this disease, immediate reduction of the environmental pressure leads to the dissolved nitrogen transforms into gas, and nitrogen bubbles form in the tissue and in the blood. These bubbles interfere the perfusion of the blood and cause ischemia. Symptoms and signs of cardiac decompression sicknesses are dyspnea, tachypnea, chest pain, cough, hemoptysis, cyanosis, retrosternal discomfort, and rarely, shock. Air embolism of coronary vessels manifests as rhythm disturbances, myocardial infarction, and circulatory collapse. The physical forces that occur because of aircraft move­ment and affect both the pilot and the aircraft, are called acceleration (G) forces. The basic physical effect of G forces is weight increments and motion restriction. During high +Gz, blood pressure decreases in the brain and increases in the lower extremities. Blood forced to move into the lower parts of the body and lower extremities. Thus, brain perfusion cannot be achieved, and loss of consciousness occurs at approximately +4 Gz acceleration levels. Earth also applies an acceleration force to the objects on or around the world. Therefore, gravitational force is also applied to orbiting spacecraft by Earth. The centrifugal force and the gravitational force are in an equilibrium, weightlessness is created inside the orbiting spacecraft, and this is called microgravity. Blood redistributed to the neck and head veins, and astronauts feel nasal fullness, and bulging around the eyes during space missions. As the time spent in the space progresses, a 22% decrease in plasma volume is observed in the cardiovascular system within 1 week owing to increased venous return, and this causes a temporary hemoconcentration. After staying one week in space, cardiac output increases by 22% whereas peripheral resistance decreases by 14%. Rhythm disturbances are also seen during activities performed in space is and thought to be caused by electrolyte imbalance or stress. There is an increasing demand for high altitude and space travel nowadays. These trips cause several physical and physiological effects on both passenger and flight crew. Therefore, it is necessary to take precautionary measures to carry out these activities safely.