The emergence of “big data,” complexities in disease etiology and therapeutics, and the reliability and validity issues in evidence discovery signals some departure from traditional foundation of statistics as a tool in data collection, processing, analysis, and interpretation. With these challenges, biostatistics needs to critically examine the following: (i) Big data and its implication in clinical decision-making in improving care and safety, (ii) reality is statistical modeling of clinical and translational research data, and (iii) tabulation/stratification versus regression model.