The second WHO report on neglected tropical diseases builds on the growing sense of optimism generated by the 2012 publication of the WHO Roadmap. Commitments on the part of ministries of health in endemic countries, global health initiatives, funding agencies and philanthropists have escalated since 2010, as have donations of medicines from pharmaceutical companies and the engagement of the scientific community.This report marks a new phase and assesses opportunities and obstacles in the control, elimination and eradication of several of these diseases. Progress over the past two years has revealed unprecedented needs for refinements in control strategies, and new technical tools and protocols. The substantial increases in donations of medicines made since the previous report call for innovations that simplify and refine delivery strategies.However, some diseases, including especially deadly ones like human African trypanosomiasis and visceral Leishmaniasis, remain extremely difficult and costly to treat. The control of Buruli ulcer, Chagas disease and yaws is hampered by imperfect technical tools, although recent developments for yaws look promising. The report highlights progress against these especially challenging diseases, being made through the development of innovative and intensive management strategies.Innovations in vector control deserve more attention as playing a key part in reducing transmission and disease burden, especially for Dengue, Chagas disease and the Leishmaniases.Achieving universal health coverage with essential health interventions for neglected tropical diseases will be a powerful equalizer that abolishes distinctions between the rich and the poor, the young and the old, ethnic groups, and women and men.