Clinical science research incorporates the fields of clinical investigation and health services research. With a focus on the use of either human specimens or subjects, clinical investigation research projects translate knowledge gained from basic science research based on animal models for disease. The goal of clinical investigation is to develop new prevention, intervention, and therapeutic approaches to improve patient clinical outcomes. In contrast, health services research focuses on the improvement of the efficacy, cost-effectiveness, and outcomes of care. Health services research projects examine options to improve the health care delivery system, organization, financing, and reimbursement mechanisms in place today. The purpose of this article is to review common terminology and methodologic approaches that are used in clinical science research. The process of designing a research project is reviewed. Beginning with the development of a research question and hypothesis, the steps for successful completion of the project are discussed. Different study design approaches are presented with their respective strengths and weaknesses. The challenges associated with conducting a clinical research study are discussed, including the development of an appropriate sampling strategy, the designing of data collection, instruments, and the assurance of study data integrity. Possible threats to study validity and generalizability are assessed.One the major advantages of clinical research is that it offers an opportunity to study clinical questions in the clinical setting without the expenses of a basic research laboratory and basic science technology. Thus important clinical questions related to patient care, new technology assessment, clinical practice management, health care administration, or health policy may be addressed.