Case-based reasoning (CBR) is an integral part of artificial intelligence. It is defined as the process of solving new problems through their comparison with similar ones with existing solutions. The CBR methodology fits well with the approach that healthcare workers take when presented with a new case, making its incorporation into a clinical setting natural. Overall, CBR is appealing in medical domains because a case base already exists, storing symptoms, diagnoses, treatments, and outcomes for each patient. Therefore, there are several CBR systems for medical diagnosis and decision support. This chapter gives an overview of CBR systems, their lifecycle, and different settings in which they appear. It also discusses major applications of CBR in the biomedical field, the methodologies used, and the systems that have been adopted. Section 13.1 provides the necessary background of CBR, while Sect. 13.2 gives an overview of techniques. Section 13.3 presents different systems in which CBR has been successfully applied, and Sect. 13.4 presents biomedical applications. A concluding discussion closes the chapter in Sect. 13.5.