The use of local and regional anesthesia in surgical practice is considered to be safe, certainly much safer than the use of general anesthesia. For example, a 1955 survey of local anesthesia used for dental procedures found only two deaths in an estimated 90 million cases over a span of 10 years [1]. Such a statistic can lull one into an inappropriate sense of security. Significant complications other than death can and do occur with the use of local anesthetics which can cause considerable difficulty for patients [2]. The incidence of adverse reactions to regional blocks in a hospital setting is approximately 0.2% [3] while the incidence of adverse responses to dental local anesthesia may be as high as 2.5% [4]. The latter figure includes a substantial number of psychological reactions. It is imperative that any physician utilizing local and regional anesthesia understand the potential risks and be prepared to manage complications. This chapter covers local and systemic adverse reactions including allergy, drug interactions, and reactions peculiar to certain drugs, and also reviews precautions that one should take to prevent difficulties.