Any new drug or entity that comes into market needs approval from regulatory agencies of the respective geography. For these approvals, there is a standardized flow of events that includes multiple phases of clinical trials, wherein the testing is performed in human volunteers or patients. While Phase 0 clinical trials are not mandatory for every drug or candidate, Phase 1 is invariably the starting point for the vast majority of drugs. In Phase 1 trials, the pool of testing is limited to a very small number of trial participants—healthy participants or patients. This phase of clinical trials focuses on “dose ranging”, wherein the ideal doses that would be safe for the end users or patients can be determined. Hence, determination of safety and the adverse effects at different doses is a priority in this phase. This chapter will elucidate the must-knows of Phase 1 clinical trials.