Oxidative stress is thought to play a significant role in the development and progression of neurodegenerative diseases. Although it is currently considered a hallmark of such processes, the interweaving of a multitude of signaling cascades hinders complete understanding of the direct role of oxidative stress in neurodegeneration. In addition to its extensive use as an aging model, some researchers have turned to the invertebrate model Caenorhabditis elegans (C. elegans) in order to further investigate molecular mediators that either exacerbate or protect against reactive oxygen species (ROS)-mediated neurodegeneration. Due to their fully characterized genome and short life cycle, rapid generation of C. elegans genetic models can be useful to study upstream markers of oxidative stress within interconnected signaling pathways. This report will focus on the roles of C. elegans homologs for the oxidative stress-associated transcription factor Nrf2, as well as the autosomal recessive, early-onset Parkinson's disease (PD)-associated proteins Parkin, DJ-1, and PINK1, in neurodegenerative processes.