The replication of positive-strand RNA viruses is a complex multi-step process involving interactions between the viral genome, virus-encoded replication factors, and host factors. The plant virus brome mosaic virus (BMV) has served as a model for positive-strand RNA virus replication, recombination, and virion assembly. This review addresses recent findings on the identification and characterization of host factors in BMV RNA replication. To date, all characterized host factors facilitate steps that lead to assembly of a functional BMV RNA replication complex. Some of these host factors are required for regulation of viral gene expression. Others are needed to co-regulate BMV RNA translation and recruitment of BMV RNAs from translation to viral RNA replication complexes on the endoplasmic reticulum. Other host factors provide essential lipid modifications in the endoplasmic reticulum membrane or function as molecular chaperones to activate the replication complex. Characterizing the functions of these host factors is revealing basic aspects of virus RNA replication and helping to define the normal functions of these factors in the host.