This first chapter describes the hazards that the space environment poses to humans, and how spaceflight affects the human body (where we are). We will then review the historical context of human spaceflight (how we got there), and end with the challenges facing humans in space (where do we go from here). Spaceflight affects every organ system in the human body, but the extent and timing of these impacts on astronaut health and performance can vary widely. The effects range from catastrophic to gradual deterioration, short-term adjustments, or even benign outcomes with no significant consequences. Space life sciences research aims to identify and document the physiological changes that occur, assess whether they meet acceptable health standards, and, if they do not, recommend updates to those standards and develop appropriate countermeasures.