Arterial chemotherapy emerged after an unintentional infusion of nitrogen mustard into the brachial artery. While the reported complications of accidental iatrogenic or self-administered arterial injections are unlikely to occur during therapeutic drug delivery, it is prudent to review these complications to learn from them. Accidental arterial drug injections can provide clues for safer drug formulations. Arterial drug injections will always carry some risk of vascular injury, thrombosis, or embolism. Thus, every effort should be made to reduce those risks. A wide-angle review of complications with arterial injections is consistent with the need to evaluate the risks and benefits of arterial delivery to avoid, detect, and promptly treat any complication.