Medical isotope generator systems are disclosed according to some aspects. In one aspect, a .sup.90Y generator system comprises a generator column, a concentration column, and a flow control system, through which the generator column and the concentration column are in fluid communication. The flow control system provides a plurality of flow configurations for delivering a milking solution to the generator column, the concentration column, or both, and for delivering an eluent solution to the concentration column in either a forward or a reverse flow direction. The generator column can comprise a .sup.90Sr stock adsorbed on a sorbent. The milking solution preferentially elutes .sup.90Y from the generator column. The concentration column comprises a sorbent that captures .sup.90Y from the milking solution without altering the milking solution. The eluent solution elutes .sup.90Y from the concentration column.