In this issue of Critical Care Clinics, guest editors Drs. Rishikesan Kamaleswaran and Andre L. Holder bring their considerable expertise to the topic of Data Science in Critical Care. Data science, the field of study dedicated to the principled extraction of knowledge from complex data, is particularly relevant in the critical care setting. In this issue, top experts in the field cover key topics such as refining our understanding and classification of critical illness using biomarker-based phenotyping; predictive modeling using AI/ML on EHR data; classification and prediction using waveform-based data; creating trustworthy and fair AI systems; and more.