Creatine monohydrate (creatine) has become an increasingly popular ingredient in dietary supplements, especially sports nutrition products. A large body of human and animal research suggests that creatine does have a consistent ergogenic effect, particularly with exercises or activities requiring high intensity short bursts of energy. Human data are primarily derived from three types of studies: acute studies, involving high doses (20 g/d) with short duration (≤1 week), chronic studies involving lower doses (3–5 g/d) and longer duration (1 year), or a combination of both. Systematic evaluation of the research designs and data do not provide a basis for risk assessment and the usual safe Upper Level of Intake (UL) derived from it unless the newer methods described as the Observed Safe Level (OSL) or Highest Observed Intake (HOI) are utilized. The OSL risk assessment method indicates that the evidence of safety is strong at intakes up to 5 g/d for chronic supplementation, and this level is identified as the OSL. Although much higher levels have been tested under acute conditions without adverse effects and may be safe, the data for intakes above 5 g/d are not sufficient for a confident conclusion of long-term safety.