Microbial fermentation processes are of great importance for the production of many bioproducts. Even for established processes, improvements in product yield, productivity, and quality are always continually demanded. This is particularly true as the products mature from being novelty to high demand, even bulk, substances, as has been witnessed for several antimicrobial compounds. High-density cultivations have been found very useful in producing a large number of modern bioproducts. Selection of the mode of fermentation, operating conditions, and optimized media are important characteristic features for high cell density, productivity, as well as the commercial success of any microbial product. This contribution reviews some of the challenges and technologies investigated for high-density cultivation. Important aspects such as medium composition, reactor conditions, oxygen transfer, temperature, agitation, pH, modes of operation, and feeding strategies for high-density cultivation are summarized in this review.