Biological control is used for management of exotic weeds but its efficacy may be variable across managed areas. Especially in cases where target weeds have large (e.g., continental) introduced distributions, biotic (e.g. competition with other agents, host quality) or abiotic (e.g. climate, moisture) factors are expected to act on introduced agents and targets differently to generate spatially heterogeneous control within the range of the agents and potentially maintain areas of enemy-free space outside their range. Biogeographic variability and incomplete distributional overlap of agents and hosts may be a common but underreported phenomenon; biological control has received little attention in this regard despite implications for understanding management failures and developing plans to improve efficacy. We reviewed the World Catalogue of Weed Biological Control and relevant literature to determine whether geographic variability in control success is common, whether variability in programs could be attributed to biotic or abiotic factors, and which regulating or limiting factors were most prevalent. Based on that review, we determined that in programs in which success varied geographically, abiotic factors such as temperature and precipitation were implicated as impacting agents most often (35% of programs), whereas 26% were at least partially due to biotic interactions such as predation or parasitism in the introduced range. In 40% of programs, the responsible factors were not reported or were unknown. In 10%, a combination of biotic and abiotic factors were reported. We discuss the various limiting and regulating biogeographic factors that contribute to spatial variability in abundance of agents and associated success of weed biological control, provide case studies and current biological control practices, and finally discuss the potential ecological and evolutionary consequences of this variability. Data to assess whether patterns of variability were predictable or to quantify variability along limiting gradients are lacking in most cases. Although a small number of programs (15%) identified more than a single factor acting to regulate impacts by introduced agents, there are almost certainly multiple important factors in most cases. Studies that address the strength of agent-host interactions across limiting gradients such as climate or precipitation may provide the best understanding of some control failures. However, investigations of other less-studied phenomena such as biotic resistance or range margin dynamics may generate valuable information and contribute to a biogeographic framework within which to evaluate ongoing and future biological control projects.