Due to their phototrophic lifestyle, cyanobacteria have been investigated as a sustainable source of biofuel production. Model cyanobacteria, such as Synechocystis, have been metabolically engineered with heterologous genes encoding pyruvate decarboxylase and alcohol dehydrogenase to convert the metabolic intermediate pyruvate first to acetaldehyde and then to ethanol. The current state of the art suggests that there is some way to go before such a system can be exploited. Lessons from the genomics of the model organism and proteomic and transcriptomic analysis of the organism's response to ethanol production are being utilised to enhance productivity. These are informing a systems approach to rational modification for enhanced ethanol production, which will be a key to the biotechnological exploitation of such a system.