From a clinical perspective, many diseases and conditions are obviously linked to the inadequate functioning of the immune system. Insufficient immune responses may produce uncontrollable acute or chronic infections. However, overt manifest responses of the immune system to infections, such as those seen in cases of septic shock or acute respiratory distress syndrome (ARDS), can also have fatal consequences. There are self-injurious responses to innocuous foreign materials or autoantigens that trigger allergies and autoimmunity problems, respectively. In addition to the classic role played in these infectious and inflammatory diseases, the immune system also plays an important role in the surveillance and control of solid tumors, hematologic malignancies, cardiovascular disease, sickle cell anemia, obesity-related health complications, and intestinal disease, for example. Consequently, knowledge of the role played by immunity in disease processes is becoming increasingly indispensable in all aspects of clinical practice. In this Special Issue we evaluate the special components of the immune system in view of the impact that immune responses have on the pathogenesis of several diseases, the targets for clinical treatments, as therapeutic agents used to control autoimmunity, either through the macanistic comparison of old and new drugs, or cell-based therapies that boost or modulate the immune system. Therefore, the objectives of this Special Issue are to check the subjects covered by Clinical Immunology, such as studies involving cases of autoimmune diseases and hematopoietic stem cell transplantation, mesenchymal stromal cells in clinical routine or in animal models, studies involving production and testing of vaccines, studies relating the manufacture of recombinant antibodies against viral infections, studies addressing the influence of commensal microbiota on immunity and tolerance, studies addressing the hormonal influence on the development or control of inflammation, preclinical studies involving models diabetes mellitus (type I preferably), psoriasis, multiple and systemic sclerosis, clinical cases and laboratory components involving inflammation in sickle cell anemia, chronic intestinal inflammation studies, and chronic skin wounds studies able to new/alternative therapeutic possibilities, not forgetting CAR T cells as tool against specific cancers.