Objective: With important technological advances in healthcare delivery and the Internet, clinicians and scientists now have access to overwhelming number of available databases capturing patients with critical illness. Yet, investigators seeking to answer important clinical or research questions with existing data have few resources that adequately describe the available sources and the strengths and limitations of each. This article reviews an approach to selecting a database to address health services and outcomes research questions in critical care, examines several databases that are commonly used for this purpose, and briefly describes some strengths and limitations of each. Data Sources: Narrative review of the medical literature. Summary: The available databases that collect information on critically ill patients are numerous and vary in the types of questions they can optimally answer. Selection of a data source must consider not only accessibility but also the quality of the data contained within the database, and the extent to which it captures the necessary variables for the research question. Questions seeking causal associations,(e.g., effect of treatment on mortality) usually either require secondary data that contain detailed information about demographics, laboratories, and physiology to best address nonrandom selection or sophisticated study design. Purely descriptive questions (e.g., incidence of respiratory failure) can often be addressed using secondary data with less detail such as administrative claims. Although each database has its own inherent limitations, all secondary analyses will be subject to the same challenges of appropriate study design and good observational research. Conclusion: The literature demonstrates that secondary analyses can have significant impact on critical care practice. While selection of the optimal database for a particular question is a necessary part of high-quality analyses, it is not sufficient to guarantee an unbiased study. Thoughtful and well-constructed study-design and analysis approaches remain equally important pillars of robust science. Only through responsible use of existing data will investigators ensure that their study has the greatest impact on critical care practice and outcomes. (Crit Care Med 2013; 41:886-896)