Microalgae have been proposed as an option for wastewater treatment since the 1960s, but still, this technology has not been expanded to an industrial scale. In this paper, the major factors limiting the performance of these systems are analysed. The composition of the wastewater is highly relevant, and especially the presence of pollutants such as heavy metals and emerging compounds. Biological and engineering aspects are also critical and have to be improved to at least approximate the performance of conventional systems, not just in terms of capacity and efficiency but also in terms of robustness. Finally, the harvesting of the biomass and its processing into valuable products pose a challenge; yet at the same time, an opportunity exists to increase economic profitability. Land requirement is a major bottleneck that can be ameliorated by improving the system’s photosynthetic efficiency. Land requirement has a significant impact on the economic balance, but the profits from the biomass produced can enhance these systems’ reliability, especially in small cities.