The family Tephritidae (order: Diptera), commonly known as fruit flies, comprises a widely distributed group of agricultural pests. The tephritid pests infest multiple species of fruits and vegetables, resulting in huge crop losses. Here, we summarize the composition and diversity of tephritid gut-associated bacteria communities and host intrinsic and environmental factors that influence the microbiome structures. Diverse members of Enterobacteriaceae, most commonly Klebsiella and Enterobacter bacteria, are prevalent in fruit flies guts. Roles played by gut bacteria in host nutrition, development, physiology and resistance to insecticides and pathogens are also addressed. This review provides an overview of fruit fly microbiome structure and points to diverse roles that it can play in fly physiology and survival. It also considers potential use of this knowledge for the control of economically important fruit flies, including the sterile insect technique and cue-lure baiting.