Resources such as fertile soil and clean water are already limited in many parts of the world. Additionally, the conventional use of arable land is becoming increasingly difficult, which is further exacerbated by climate change. Soilless cultivation systems do not only offer the opportunity to save water and cultivate without soil but also the chance to open up urban areas such as residential rooftops for food production in close proximity to consumers. In this review, applications of soilless farming systems are identified and compared to conventional agriculture. Furthermore, aspects of economic viability, sustainability and current developments are investigated. An insight into the most important soilless farming systems—hydroponics, aquaponics and vertical farming—is provided. The systems are then differentiated from each other and, as far as possible, evaluated in terms of their environmental impact and compared with conventional cultivation methods. Comparing published data analyzing the yield of hydroponic cultivation systems in comparison to soil-based cultivation methods enables a basic overview of the profitability of both methods and, thus, lays the foundation for future research and practical applications. The most important inert substrates for hydroponic applications are presented, and their degree of sustainability is compared in order to emphasize environmental impacts and affect substrate selections of future projects. Based on an assessment of the most important soilless cultivation systems, the challenges and developments of current techniques are highlighted and discussed.