Performing experiments in space is an expensive and time-consuming process. An investigator would be extremely fortunate to fly one experiment a year for several years in a row. For this reason, scientists are constantly looking for ground-based models that simulate the effects of microgravity on their experimental subjects. Although no ground-based model can perfectly simulate the effects of microgravity, models allow scientists to gather preliminary data and expand their knowledge of certain phenomena observed in space without the cost or complication of a space flight experiment. This Special Topic at SpaceBio provides an overview of various ground-based models.