This Note analyzes the relationship between “malice aforethought,” the mens rea required to commit murder, and self-defense, a potential justification for a killing. Although both concepts are well-established in criminal law, there is a dearth of jurisprudence dealing with their intersection. Specifically, many jurisdictions, including the Second Circuit, have yet to conclusively address the issue of whether the mental state required for proving a self-defense justification is incompatible with the mens rea of malice aforethought required for committing murder under the primary federal murder statute, 18 U.S.C. § 1111. Because under federal law, self-defense is an issue of common law, rather than statutory, the existing case law on this question in federal jurisdictions is inconsistent, inconclusive, and often nonexistent. Some circuits have indicated, often in dicta, that malice is incompatible with the reasonable fear for one’s safety that is required when acting in self-defense, while other courts have found it consistent for a defendant to possess a preformulated intent to kill another person but also act (and therefore kill) in the moment due to a fear for his or her life or safety. While both positions present analytical difficulties, these problems all stem largely from the definitional ambiguity surrounding “malice aforethought” and courts’ subsequent inconsistent applications of the concept in murder trials. Therefore, this Note argues for the adoption of a clear and consistent definition of “malice aforethought” which encompasses its common law definition, requiring a depraved or evil mental state beyond mere intent to kill.