Countermeasures to prevent or partially offset the negative physiologic changes that are caused by the effects of microgravity play an important role in supporting the performance of crewmembers in flight and their safe return to Earth. Research conducted in Russia on the orbital stations Salyut and Mir, as well as simulation experiments on the ground, have demonstrated that changes that occur during extended spaceflight in various physiologic systems can be prevented or significantly decreased by using countermeasures. Hardware and techniques used on the ISS have been substantially improved to reflect the experience of previous extended missions on Russian orbital stations. Countermeasures used during early ISS missions consisted of the U.S. treadmill (TVIS), cycle ergometer (ВБ-3), a set of resistance bands, a postural muscle loading suit (Penguin-3), electrical stimulator (Tonus-3), compression thigh cuffs (Braslet-М), a lower body negative pressure (LBNP) suit (Chibis), a lower body g-loading suit (Kentavr), and water/salt supplements. These countermeasures are described in this article.