To facilitate their replication flaviviruses remodel cytoplasmic host membranes to induce the formation of the viral replication complex (RC). These membranous structures are derived from the endoplasmic reticulum and are comprised of multiple host proteins and lipids and specific viral proteins. Previously we have observed that the viral protein NS4A alone can induce the formation of a subset of these membranes in the absence of other viral proteins and that the host lipids cholesterol and ceramide play important roles during replication, although there is differential utilization of some of these components between different flaviviruses. We have now extended our studies to include other phospholipid species and host proteins that facilitate intracellular flavivirus replication but again show that West Nile, Dengue and Zika viruses may form a RC with shared components but in three different ways.