After a less dynamic period, space exploration is now booming. There has been a sharp increase in the number of current missions and also of those being planned for the near future. Microorganisms will be an inevitable component of these missions, mostly because they hitchhike, either attached to space technology, like spaceships or spacesuits, to organic matter and even to us (human microbiome), or to other life forms we carry on our missions. Basically, we never travel alone. Therefore, we need to have a clear understanding of how dangerous our “travel buddies” can be; given that, during space missions, our access to medical assistance and medical drugs will be very limited. Do we explore space together with pathogenic microorganisms? Do our hitchhikers adapt to the space conditions, as well as we do? Do they become pathogenic during that adaptation process? The current review intends to better clarify these questions in order to facilitate future activities in space. More technological advances are needed to guarantee the success of all missions and assure the reduction of any possible health and environmental risks for the astronauts and for the locations being explored.