Neglected diseases have been characterised as a misalignment in the research system because so little research is directed towards such a large burden of disease. By focusing on one of the most extreme cases of misalignment, we highlight opportunities and potential pitfalls of targeting research towards specific social outcomes more generally.We trace how the category of neglected diseases came to prominence, largely framed as a problem to be addressed by scientific research. This mobilised R&D investment but there have been unintended consequences, particularly for broader health system strengthening and research capacity building efforts.These developments may contribute to a 'tragedy of the evaluation commons', where the effectiveness of broad remit research programs remain poorly characterised. This exacerbates a lack of evidence, relative to targeting specific diseases where the evaluation challenge is narrower. Research targeting then, is intimately tied to evaluation practice. A new research and policy agenda oriented towards broader research evaluation may support further investments not just for biomedical R&D in high-income countries, but also for researchers in other countries, for interdisciplinary, applied and social sciences, and ultimately, for poor patients.