This paper offers a review on different experiences that have been conducted in South America, which are of interest for the agricultural use of the brine reject originated in inland desalination plants. The results obtained by a combined production scheme that uses brine reject from inland desalination plants for fish farming and for the irrigation of halophyte forage shrubs are summarized. This scheme has succeeded in turning an environmental problem (the brine reject disposal in inland areas) into a source of new economical activities. However, despite a slightly salt removal capacity shown by the halophytes, this production scheme was not able to prevent a progressive salinization of the land irrigated with the reject brine. The yields obtained are analyzed in terms of fish and forage production as well as the weight gain in the livestock fed with the halophytes. Also, due to its characteristics and good performance in arid regions and saline waters, the cultivation of Spirulina cyanobacteria is proposed as an alternative for fish farming within this production scheme. Finally, a series of South American studies addressing the irrigation of crops under saline conditions are reviewed, with the objective of establishing their potential use for reject brine management.