Since the founding of PLOS Neglected Tropical Diseases more than six years ago, I have written about the interface between disease and geopolitics. The neglected tropical diseases (NTDs) are the world’s most common infections of people living in poverty. Where they are widespread in affected communities and nations, NTDs can be highly destabilizing and ultimately may promote conflict and affect international and foreign policy. Many of the published papers in this area were recently re-organized in a PLOS “Geopolitics of Neglected Tropical Diseases” collection that was posted on our website in the fall of 2012, coinciding with the start of our sixth anniversary. From this information, a number of new and interesting findings emerged about the populations who are most vulnerable to the NTDs, including the extreme poor who live in the large, middle-income countries and even some wealthy countries (such as the United States) that comprise the Group of Twenty (G20) countries, as well as selected Aboriginal populations. Together, the PLOS “Geopolitics of Neglected Tropical Diseases” collection and the G20 analyses identified more than a dozen areas of the world that repeatedly show up as ones where NTDs disproportionately affect the poorest people living at the margins. Here, I summarize what I view as ten of the worst global “hotspots” where NTDs predominate. They represent regions of the world that will require special emphasis for NTD control and elimination if we still aspire to meet Millennium Development Goals (MDGs) and targets by 2015; they are regions that may need to be highlighted again as we consider post-MDG aspirations and new Sustainable Development Goals (SDGs).