Firstly, at high solids loading of typically 15-30 (w/w) %, high viscosity prevail leading to poor mixing and therefore large deviation in local conditions in the fermentor. The high solid content may also have a direct influence on the enzymes and microorganisms. Secondly, high concentrations of inhibitory compounds will typically be present leading to poor cellular performance and cell viability problems. In our research group we address these problems both by developing the fermentation strategies and through strain improvement. In this presentation, insights from physiological behavior at high solids condition will be discussed in light of designing fermentation strategies suitable for high solid conditions. To tackle the cell viability problems at high solids, evolutionary engineering was applied to improve the cellular performance. Furthermore, studies for increasing the understanding of the importance of cell propagation for fermentation performance were pursued.