Clinical decision support systems rely on automated reminders to warn clinicians of potentially harmful drug interactions and to promote appropriate therapy. However, studies have shown that many alerts are relatively inconsequential—one study found that nearly 300 reminders were required to prevent one adverse drug event. This problem leads to alert fatigue on the part of clinicians, but thus far, system developers have been reluctant to tailor alerts to maximize yield, due to concerns about liability if alerts are removed. Reviewing the legal issues around decision support systems, this commentary advocates for stronger regulation and guidelines to allow greater tailoring of alerts to minimize alert fatigue and improve the safety performance of decision support systems. A recent consensus conference identified the key issues in developing more effective alert mechanisms.