Establishing the first human presence on Mars will be the most technically challenging undertaking yet in the exploration beyond our planet. The remoteness of Mars from Earth, the inhospitable surface conditions including low atmospheric pressure and cold temperatures, and the need for basic resources including water, pose a formidable challenge to this endeavour. The intersection of multiple disciplines will be required to provide solutions for temporary and eventually permanent Martian habitation. This review considers the role cyanobacteria and eukaryotic microalgae (collectively referred to here as 'microalgae') may have in supporting missions to the red planet. The current research using these microorganisms in biological life support systems is discussed, with a systematic analysis of their usage in each system conducted. The potential of microalgae to provide astronauts with oxygen, food, bio-polymers and pharmaceuticals is considered. An overview of microalgal experiments in space missions across the last 60 years is presented, and the research exploring the technical challenges of cultivation on Mars is discussed. From these findings, an argument for culturing microalgae in subterranean bioreactors is proposed. Finally, future synthetic biology approaches for enhancing the cyanobacterial/microalgal role in supporting human deep-space exploration are presented. We show that microalgae hold significant promise for providing solutions to many problems faced by the first Martian settlers, however these can only be realised with significant infrastructure and a reliable power source.