Subcutaneous immunotherapy (SCIT), commonly referred to as “allergy shots,” is an important component of allergic care in patients who fail to respond adequately to medical management. Rather than just decreasing symptoms, immunotherapy has the potential to modify the allergic response long term through desensitization. This can result in significant improvements in allergy-mediated symptoms. While well-controlled clinical trials support the efficacy of SCIT, there are variations in how SCIT is utilized in clinical practice related to antigen selection, number of antigens used, and antigen preparation. This chapter describes the history of SCIT, supporting evidence, and important considerations regarding considerations that lead to differences in how SCIT is applied in practice. Patient considerations such as mono- versus poly-sensitization, contraindications, and key components of the shared decision-making process. Vial mixing and SCIT injection schedules are also reviewed.