Many organisms, including humans and the yeast S. cerevisiae, experience hypoxia, or low oxygen. To adapt to this new environment, cells employ signaling pathways to mount a global change in gene expression. In S. cerevisiae, previous studies have focused on the mechanisms of individual pathways but how multiple pathways together mount a large hypoxic response is not well understood. Here, we attempt to identify and characterize all signaling pathways that contribute to the hypoxic response. We propose at least seven signaling pathways composed of 19 genes that mediate the response, with many genes conserved in humans. To study the role of each signaling gene, we have created single deletion strains. To study each pathway, we have created “pathway” mutant strains that contain deletions of all the genes in a pathway. Studying these strains will help delineate the contribution of each pathway and also reveal redundancy in the signaling network. Surprisingly, all of the strains can grow during hypoxia, suggesting that the signaling genes may be important for long-term survival or fitness in hypoxia. To test the role of the signaling genes and pathways in the gene expression response, each strain was subjected to an anaerobic environment for 5, 10, 30, 60, 120, 180, and 240 minutes. RNA was extracted from the cells and mRNA level was determined by RNA-Seq and RT-qPCR analyses. First, we described the wildtype hypoxic response by employing three statistical tests to identify the genes that exhibited a robust time-dependent response. The first test employs DESeq to identify the genes that fit a quadratic when comparing expression to time. The second uses autocorrelation as a measure of the smoothness of a gene’s response, and the third compares the means of early vs. late time points to isolate large expression changes over time. A total of 715 genes were identified including almost all of the expected oxygen-regulated genes as well as previously undiscovered genes. Additionally, we found that the hypoxic response is distinct from the environmental stress response and appears to represent a transition to a new growth state. By observing the gene expression response in some of the mutants, we have found that multiple signaling pathways are indeed responsible and that there is redundancy in the response network. This work contributes to our understanding of a large cellular response that involves the coordination of several signaling pathways.