Microalgae are sustainable feedstock for healthy food and feed, organic drugs, ecological polymers, green chemicals and dyes, biofuels, biofertilizers, and environmental bioremediation technologies. Despite its enormous promises, microalgae cultivation is expensive and thus large-scale production is centred on low volume/high value markets, such as the specialty food and feed, dietary supplements and pharmaceuticals. Large-scale microalgal cultivation is severely limited by the low biomass productivity achieved in current production systems, due to low photosynthetic efficiency. Furthermore, the management of carbon dioxide (CO 2 ) for microalgal large-scale production is costly and faces technological constraints. The cultivation of microalgae in media supplemented with organic carbon substrates, with or without light, can significantly increase biomass productivities and overcome the technical constraints associated to CO 2 supply. This review collects quantitative data to compare microalgal autotrophic growth and metabolite accumulation with heterotrophic, mixotrophic and photoheterotrophic cultivation modes. Critique hypotheses are proposed to explain the increase in biomass productivity once microalgae are supplied with organic carbon molecules. The main cultivation parameters that could affect biomass accumulation are also analysed. Supplementation of microalgae with organic carbon substrates could be a suitable strategy towards a microalgal economy, despite the constraints and challenges that have to be overcome and that are also analysed. • Large-scale microalgal cultivation is constrained by low biomass productivities. • Photosynthetic efficiency is low in autotrophic production systems. • Large-scale management of carbon dioxide faces economic and technical constraints. • Microalgal biomass productivities can be increased with organic carbon substrates. • Selection of growth model is critical for successful microalgae production system.