Major municipal wastewater reclamation plants in California, USA, Singapore, and many built or planned for other regions of the world use the high pathogen reduction properties of microfiltration/ultrafiltration (MF/UF) membranes followed by reverse osmosis (RO) membranes. Operational experiences in these plants suggest that while MF and UF membranes encounter pore and cake fouling by colloidal particles (0.1 micron down to molecular sizes, ie. nanoparticles), a significant fraction of the smaller colloidal particles pass through the MF and UF membranes, and end up on RO membranes as cake-layer foulants. Autopsies, foulant analyses and cleaning studies performed on fouled RO membranes from the plants and pilot plants showed that colloidal natural organic matter, colloidal calcium phosphate and some times colloidal silicates are the main components. These colloidal particles have great affinity towards aggregation with each other. Due to incomplete removal by MF and even UF, fouling of RO membranes downstream becomes measurable by trend-charts of normalized values of permeate flow, differential pressure and salt passage. Normalized permeate flow is the most sensitive, and an early indicator of such fouling. In this paper we will provide some details of our studies and provide literature evidences that support the conclusion that calcium phosphate in foulants originated as nanoparticles in the wastewater.