One of the main goals of bioprocess engineering is to increase the productivity of biotechnological processes and a vigorous progress has been observed in that field over the last decades. Fermentation based processes are not an exception and, in order to achieve those objectives, techniques such as the use of high cell density systems have been proposed and studied. The interest for such systems is increasing for they seem to be a very promising alternative to the traditional cell suspension fermentation. In fact, they may increase volumetric productivity, product concentrations in the outlet and conversion of raw materials, as a higher biomass concentration (biocatalyst) is present, at any moment, inside the bioreactor. Downstream processing will also be improved by the use of these technologies, as smaller amounts of biomass will be present in the effluent of the bioreactor. To achieve this, several new processes were studied, changes in existing ones were introduced and technical developments were made. The examples are various and cover diverse applications such as ethanol, beer and antibiotics production, and waste water treatment, just to quote a few representative areas. Among the several immobilisation techniques, flocculation, although not being extensively considered, is one of the most attractive. In this chapter, the main aspects associated with high cell density cultures using flocculating microorganisms will be considered. Aspects such as bioreactor design and performance, mass transfer limitations in cell aggregates and their relation with yeast cell activity, as well as applications, will be considered and discussed.