This monograph focuses on understanding statistical and clinical significance and is one in a research and statistics series published by the statistical team of the Journal of the Academy of Nutrition and Dietetics. The content covers the research questions, definition of clinical significance, hypothesis testing, P values, effect sizes, sample sizes, CIs, power analyses, minimal clinically important differences, and validity. This monograph concludes with a summary of the importance of clinical and statistical results for credentialed nutrition and dietetics practitioners to consider when assessing statistical and clinical significance.