The often-observed higher emission of nitrogen oxides with biodiesel, relative to petroleum diesel, is well-reported in the literature. Upon review of the literature, there seem to be two broad contributors that cause such a trend: those that are manifested by the effects of fuel property differences directly on in-cylinder processes and those that are manifested by the effects of fuel property differences on engine systems, thus rendering an indirect effect on in-cylinder processes. In this article, the former manifestations are called fundamental issues while the latter manifestations are called system response issues. Both can have significant impact on the magnitude and direction of nitrogen oxides emission differences between biodiesel and petroleum diesel fuels. This article has the objective to identify the distinction between fundamental and system response issues on nitric oxide emissions of biodiesel combustion in a diesel engine. It is noted that the article focuses mostly on the system response issues of a production-type engine, and will only briefly summarize some of the fundamental issues believed to most strongly contribute toward differences in nitric oxide emissions between fuels. Consequently, it is important to note (in fact, a major theme of the article) that many of the specific observations of this study will not necessarily transcend to generality across all engine platforms due to differences in engine technology and calibration; instead, the emphasis on the important role of potential system responses manifested by the use of different fuels of any engine system is meant to be the general contribution of this study. The study generally observes that biodiesel, in the absence of system response issues, emits higher NO x than petroleum diesel. System response issues, however, can have a dramatic impact on biodiesel NO x emissions. In some cases, system response issues may cause biodiesel NO x to be lower than petroleum diesel. Such system response issues highlight potential opportunities to mitigate or decrease biodiesel NO x emissions relative to petroleum diesel.