Wolbachia are gram-negative bacteria that are widespread in nature, carried by the majority of insect species as well as some mites, crustaceans, and filarial nematodes. Wolbachia can range from parasitic to symbiotic, depending upon the interaction with the host species. The success of Wolbachia is attributed to efficient maternal transmission and manipulations of host reproduction that favor infected females, such as sperm-egg cytoplasmic incompatibility (CI). Much remains unknown about the mechanistic basis for Wolbachia-host interactions. Here we summarize the current understanding of Wolbachia interaction with insect hosts, with a focus on Drosophila. The areas of discussion include Wolbachia transmission in oogenesis, Wolbachia distribution in spermatogenesis, induction and rescue of the CI phenotype, Wolbachia genomics, and Wolbachia-membrane interactions.