Various techniques to block the brachial plexus are employed to provide surgical anesthesia and superior analgesia for operative interventions and pain conditions in the upper extremity, helping avoid the risks and side effects of general anesthesia and high-dose opioids. However, the anesthesiologists should also be familiar with the possible associated complications, including nerve damage, inadequate blockade, bleeding, local anesthetic systemic toxicity, diaphragmatic paralysis, pneumothorax, and the potential of masking the clinical picture of acute compartment syndrome. Prevention, early detection and correct diagnosis, as well as prompt and adequate management of each complication, are critical and require considerable fundamental knowledge, clinical skills and experience. Safety of regional anesthesia also depends on consistent implementation of standards of care, based on constantly updated best practices. This chapter attempts to illustrate the role of brachial plexus blockade in caring for patients undergoing surgery of the upper extremity, focusing on common associated scenarios, decision-making, troubleshooting and crisis management. It offers a brief review of relevant anatomy and pathophysiology, describes clinical management of important complications ranging from shortness of breath and nonfunctioning block to cardiac arrest. It provides basis for understanding various related events, to be shared and collaboratively addressed by the entire perioperative team.