  Since the introduction of Direct Electron Detectors (DEDs), the resolution
and range of macromolecules amenable to this technique has significantly
widened, generating a broad interest that explains the well over a dozen
reviews in top journal in the last two years. Similarly, the number of job
offers to lead EM groups and/or coordinate EM facilities has exploded, and FEI
(the main microscope manufacturer for Life Sciences) has received more than 100
orders of high-end electron microscopes by summer 2016. Strategic corporate
movements are also happening, with very big players entering the market through
key acquisitions (Thermo Fisher has recently bought FEI for \$4.2B), partly
attracted by new Pharma interest in the field, now perceived to be in a
position to impact structure-based drug design. The scientific perspectives are
indeed extremely positive but, in these moments of well-founded generalized
optimists, we want to make a reflection on some of the hurdles ahead us, since
they certainly exist and they indeed limit the informational content of cryoEM
projects. Here we focus on image processing aspects, particularly in the
so-called area of Single Particle Analysis, discussing some of the current
resolution and high-throughput limiting factors.
