We conclude this special issue on the Global Earthquake Forecasting System (GEFS) by briefly reviewing and analyzing the claims of non-seismic precursors made in the present volume, and by reflecting on the current limitations and future directions to take. We find that most studies presented in this special volume, taken individually, do not provide strong enough evidence of non-seismic precursors to large earthquakes. The majority of the presented results are hampered by the fact that the task at hand is susceptible to potential biases in data selection and possible overfitting. The most encouraging results are obtained for ground-based geoelectric signals, although the probability gain is likely small compared to an earthquake clustering baseline. The only systematic search on satellite data available so far, those of the DEMETER mission, did not find a robust precursory pattern. The conclusion that we can draw is that the overall absence of convincing evidence is likely due to a deficit in systematically applying robust statistical methods and in integrating scientific knowledge of different fields. Most authors are specialists of their field while the study of earthquake precursors requires a system approach combined with the knowledge of many specific characteristics of seismicity. Relating non-seismic precursors to earthquakes remains a challenging multidisciplinary field of investigation. The plausibility of these precursors predicted by models of lithosphere-atmosphere-ionosphere coupling, together with the suggestive evidence collected here, call for further investigations. The primary goal of the GEFS is thus to build a global database of candidate signals, which could potentially improve earthquake predictability (if the weak signals observed are real and false positives sufficiently uncorrelated between different data sources). Such a stacking of disparate and voluminous data will require big data storage and machine learning pipelines, which has become feasible only recently. This special issue compiled an eclectic list of non-seismic precursor candidates, which is in itself a valuable source of information for seismologists, geophysicists and other scientists who may not be familiar with such types of investigations. It also forms the foundation for a coherent, multi-disciplinary collaboration on earthquake prediction.