Systems and methods related to desalination systems are described herein. According to some embodiments, the desalination systems are hybrid systems comprising one or more first desalination units and one or more second desalination units. In some embodiments, the one or more second desalination units, which may form a fluidic circuit that is located downstream from the one or more first desalination units, may be configured to desalinate higher salinity liquid streams than the one or more first desalination units. In certain embodiments, the one or more first desalination units are operated under steady-state conditions and/or configured to operate under steady-state conditions. In certain embodiments, the one or more second desalination units are transiently operated and/or configured to facilitate transient operation. In some embodiments, a liquid stream comprising water and at least one dissolved salt is flowed through the one or more first desalination units, which are configured to remove at least a portion of the water from the liquid stream to form a first concentrated brine stream enriched in the dissolved salt. In some embodiments, at least a portion of the first concentrated brine stream is fed to a fluidic circuit comprising the one or more second desalination units. In some embodiments, the one or more second desalination units are configured to remove at least a portion of the water from the first concentrated brine stream to produce a second concentrated brine stream further enriched in the dissolved salt. In certain cases, the second concentrated brine stream is recirculated through at least a portion of the fluidic circuit until the second concentrated brine stream reaches a relatively high density (e.g., at least about 10 pounds per gallon) and/or a relatively high salinity (e.g., a total dissolved salt concentration of at least about 25 wt %).