Microorganisms on synthetic membranes cause biofouling. Reviewing the microorganisms involved in biofouling shows that membrane filtration provides a selective environment for bacteria and archaea, but not for fungi. Investigation of 21 Sphingomonadaceae bacteria, isolated from fouled membranes, shows that their growth requirements are irreconcilable with family members isolated from other environments. Studying membrane fouling under axenic yet representative conditions, illustrates that considerable differences in membrane performance emerge due to the stochastic nature of biofilm formation. The outcomes also indicate that there is no correlation between surface adhesion and membrane fouling. Repetitive cleaning leads to a stable, resilient bacterial biofilm community on the membrane with increased mechanical tolerance against membrane flushing. We conclude that, to control membrane fouling, the best way forward is to combine antifouling strategies with different modus operandi.