The cost of seawater desalination by reverse osmosis technology (RO) continues to drop with time. This portends accelerating adoption of RO around the world in the 21st century. Since chemicals are used in the operation of RO systems as coagulants, antifoulants and cleaners, continuing and increasing the adoption of the RO process in the Gulf necessitates conservation and efficient utilization of these chemicals. This is possible through understanding and optimization of the RO process chemistry. In this paper we survey the chemical factors that affect the operational characteristics of RO systems. The factors include the chemistry of the feedwater, membrane fouling mechanisms, composition of foulants found in membrane elements from many plants around the world and examples of antifoulants and their application. Current approaches towards the development of antifoulants to prevent fouling and membrane cleaners for plant maintenance are discussed in this context. The chemistry presented is part of a conceptual framework in which process optimization and chemical usage conservation can progress well into the next century.