The 50/500 rule has been used as a guiding principle in conservation for assessing minimum viable effective population size (Ne). There is much confusion in the recent literature about how the 500 value should be applied to assess extinction risk and set priorities in conservation biology. Here, we argue that the confusion arises when the genetic basis for a short-term Ne of 50 to avoid inbreeding depression is used to justify a long-term Ne of 500 to maintain evolutionary potential. This confusion can result in misleading conclusions about how genetic arguments alone are sufficient to set minimum viable population (MVP) thresholds for assessing the extinction risk of threatened species, especially those that emphasize that MVPs should be in the thousands to maintain evolutionary potential.