This article focuses on the most important diseases of dairy calves and heifers and presents clinical approaches that can improve detection, diagnosis, and treatment of herd-based problems. A systematic herd investigation strategy is pivotal to define the problems, understand important risk factors, develop a plan, and make recommendations for disease management accurately. A review of records, colostrum and feeding routines, housing and bedding management, routine procedures, vaccination, and treatment protocols begins the investigation and determines which diagnostic procedures and testing strategies are most useful. Disease management is most effective when the problem source is well defined and the exposure can be limited, calf immunity can be enhanced, or a combination of both. Screening examinations performed regularly or done at strategic time points improves detection of disease, can be used to monitor treatment outcomes, and can avoid disease outbreaks.