Much of its course is owned and operated by the Bexar-Medina-Atascosa Water District to provide irrigation services to farmers and ranchers.

It once served as the official boundary between Texas and Coahuila[2] with the San Antonio River being considered its tributary.

Much of the source water to the Medina River is produced by springs emerging due to the presence of the Balcones Fault.

For example, species such as the California Fan Palm, Washingtonia filifera, occur only west of the Medina River or Balcones Fault.

[3] The Medina River once received significant waste discharge from upstream catfish farming operations, which utilized more water than was sustainable to the basin's safe usage.