Cyanobacteria evolved the oxygenic photosynthesis to generate organic matter from CO2 and sunlight, and they were responsible for the production of oxygen in the Earth's atmosphere. This made them a model for photosynthetic organisms, since they are easier to study than higher plants. Early studies suggested that only a minority among cyanobacteria might assimilate organic compounds, being considered mostly autotrophic for decades. However, compelling evidence from marine and freshwater cyanobacteria, including toxic strains, in the laboratory and in the field, has been obtained in the last decades: by using physiological and omics approaches, mixotrophy has been found to be a more widespread feature than initially believed. Furthermore, dominant clades of marine cyanobacteria can take up organic compounds, and mixotrophy is critical for their survival in deep waters with very low light. Hence, mixotrophy seems to be an essential trait in the metabolism of most cyanobacteria, which can be exploited for biotechnological purposes.