For the fatigue design of aluminum structures, most applicable international codes specify fatigue-resistance (S-N) curves with slopes that vary, depending on the detail category. This complicates the selection of appropriate damage equivalence factors for use in highway bridge applications. The existing codes also differ in their treatment of high cycle fatigue, with single-slope S-N curves specified in some cases and multislope curves specified in others. In this paper, a recent investigation conducted to examine the fatigue behavior of aluminum welds under in-service highway bridge loading conditions is summarized. Specifically, calculations performed to establish damage equivalence factors for aluminum for use with the AASHTO and Canadian Standards Association (CSA) CAN/CSA-S6 codes are first reviewed. Following this, small-scale fatigue tests of aluminum welds under simulated highway bridge loading conditions are described. A fracture mechanics model is then validated by comparison with the test results and used to perform simulations encompassing a wider range of loading conditions. On the basis of this work, the adequacy of the current design provisions is discussed and possibilities for further extending the employed methodology are identified.