The cell contains highly dynamic structures exploiting physical principles of self-organisation at the mesoscale (100 nm to 10 μm). Examples include non-membrane bound cytoplasmic bodies, cytoskeleton-based motor networks and multi-scale chromatin organisation. The challenges of mesoscale self-organisation were discussed at a CECAM workshop in July 2014. Biologists need approaches to observe highly dynamic, low affinity, low specificity associations and to perturb single structures, while biological physicists and biomathematicians need to work closely with biologists to build and validate quantitative models. A table of terminology is included to facilitate multidisciplinary efforts to reveal the richness and diversity of mesoscale cell biology.