The United States Constitution's Fifth and Sixth Amendments protect the rights of criminal defendants and witnesses. The Fifth Amendment's privilege against self-incrimination protects witnesses from forced self-incrimination, and the Sixth Amendment provides criminal defendants with the right to cross-examine prosecution witnesses and to have compulsory process for obtaining witnesses. These fundamental rights conflict when a prosecution witness invokes the Fifth Amendment privilege on cross-examination or when a defense witness invokes the privilege on direct-examination. A grant of either use or transactional immunity would remove the potential for self-incrimination, but courts are split on whether they possess the authority to grant such immunity to defense witnesses. This Note examines the judicial approaches to resolving the conflicts between the Fifth and Sixth Amendment, and it analyzes the factors that favor and those that oppose a grant of immunity to defense witnesses. This Note concludes that defense witnesses should be granted use immunity whenever their testimony might be exculpatory.