Reverse osmosis and nanofiltration systems are continuously challenged with biofouling of polyamide membranes that are used almost exclusively for these desalination techniques. Traditionally, pretreatment and reactive membrane cleanings are employed as biofouling control methods. This in-depth review paper discusses the mechanisms of membrane biofouling and effects on performance. Current industrial disinfection techniques are reviewed, including chlorine and other chemical and non-chemical alternatives to chlorine. Operational techniques such as reactive membrane cleaning are also covered. Based on this review, there are three suggested areas of additional research offering promising, polyamide membrane-targeted biofouling minimization that are discussed. One area is membrane modification. Modification using surface coatings with inclusion of various nanoparticles, and graphene oxide within the polymer or membrane matrix, are covered. This work is in the infancy stage and shows promise for minimizing the contributions of current membranes themselves in promoting biofouling, as well as creating oxidant-resistant membranes. Another area of suggested research is chemical disinfectants for possible application directly on the membrane. Likely disinfectants discussed herein include nitric oxide donor compounds, dichloroisocyanurate, and chlorine dioxide. Finally, proactive cleaning, which aims to control the extent of biofouling by cleaning before it negatively affects membrane performance, shows potential for low- to middle-risk systems.