The growing global demands for freshwater are increasing the volumes of brine produced through desalination processes. However, brine discharge into the environment, if not properly treated, can cause adverse ecological impacts due to its high saline content. Minimal liquid discharge (MLD) and zero liquid discharge (ZLD) systems have emerged as promising strategies to reduce brine pollution risks while enabling water reuse and resource recovery. This chapter examines the opportunities and challenges of adopting MLD and ZLD approaches through a biotechnological lens. It provides background on the problems created by uncontrolled brine discharge and the need to develop sustainable brine management solutions. The chapter then discusses various membrane-based and thermal-based technologies that can be deployed in MLD and ZLD systems to separate freshwater from brine through techniques like concentration, evaporation, and crystallization. It highlights some emerging technologies showing potential to improve the efficiency and energy demands of MLD and ZLD processes. The key differences between MLD and ZLD configurations and their relative sustainability benefits are also examined. Overall, the chapter demonstrates how biotechnological applications of MLD and ZLD can effectively address brine treatment while facilitating valuable resource recovery from this waste stream.