Insect stings can cause large local reactions (LLRs) that are IgE-mediated and associated with considerable morbidity. A risk for systemic reactions including anaphylaxis to subsequent stings has been reported and is often noted by patients and health care providers. Guidelines do not recommend venom immunotherapy (VIT) for LLRs based on the relatively low risk of anaphylaxis, but this is debated in this review. On the pro side: the risk of anaphylaxis may be higher than reported in the limited literature, especially in patients who had only 1 LLR; new species with more potent stings are spreading into new areas; the quality of life can be markedly impaired by LLRs; and VIT is generally safe and highly effective. On the con side: LLRs are benign, stings occur infrequently, VIT has significant cost, systemic reactions occur more often to VIT than to stings in patients with LLRs, and Food and Drug Administration approval and published guidelines do not recommend VIT for LLRs. In practice, shared decision-making is appropriate to incorporate knowledge of the natural history and known high-risk factors in the context of the patient's personal values and preferences.