Anaerobic sludge bed reactor systems like the upflow anaerobic sludge blanket (UASB) and expended granular sludge bed (EGSB) reactors are currently the mostly applied high-rate reactor systems for anaerobic wastewater treatment. The success of both systems has changed the world conception of wastewater treatment with energy recovery being an intrinsic part of the treatment process, avoidance of excess sludge problems and extremely low space requirement. Nevertheless, while broadening the UASB reactor application to a diverse type of wastewaters, high salinity wastewaters were found to give an adverse effect to the granulation processes. Accumulation of Na+ at high concentrations produced weaker and fluffy granules endangering the applicability of the mentioned sludge bed systems. In this thesis, research was conducted to investigate the mechanisms of destabilization of the granules at high Na+ concentrations, while trying to improve the granules' properties. Chapter 1 gives an overview of high salinity wastewaters, the application and the bottlenecks of anaerobic wastewater treatment (AnWT) technology under extreme conditions. Focus is given to the granulation process as a key factor in the operation of high rate anaerobic reactors. Indeed, it is a complex process that involves physicochemical as well as biological mechanisms. A short overview of the previous research on anaerobic wastewater treatment processes for high salinity wastewaters is discussed, followed by granulation theories and processes. Referring to the imbalance in the monovalent to divalent cation ratio, the Ca 2+ augmentation approach is discussed in this chapter as a tool to establish a favourable ratio for the required granulation process. The chapter also discusses the need for extracellular polymeric substances (EPS) production, depending on the types of substrates, as a major factor for a successful granulation process. Specifically for high Na+ concentrations, also the importance of K+ and more specifically the K+/Na+ ratio is discussed as a control regulator to alleviate the negative effects of Na+. Finally, the review discusses microbiological aspects related to the anaerobic treatment of high salinity wastewaters such as the adaptation of sludge to high Na+ concentrations and the presence of halophilic/halotolerent microorganisms and their application in anaerobic wastewater treatment.