Musical expression is a characteristic of humanity on Earth. This paper highlights the historical relationship between music and spaceflight, including its use in the representation of space, and its role in space culture. The paper documents circa 57 musical instruments: from a miniaturized harmonica to a 1.5 m Digeridoo that are known to have been taken into space – usually as part of a crew members personal allowance. Due to mass and volume restrictions numerous classical and ethnographic instruments have been ‘spaceflight-adapted’, in addition to the use of digital technologies for personal musical pleasure and public relations. Furthermore, it charts how access to personalised music playlists and shared musical experiences have been deemed to be vital by crew, promoting individual wellbeing including a connection to home, to each other and playing a part in the marking of success, and tragedy. The value of music making in space is briefly described leading to the proposition that as humanity ventures with greater regularity to Low Earth Orbit and beyond, consideration of how music can be effectively utilised to support individual and crew wellbeing, whilst contributing to the cannon of human artistic expression is warranted.