The last ten years have seen an unprecedented merge of physiology and genomics. While the field of physiological genomics is still very young, the introduction of the concept of systems biology promises to propel physiological genomics to a whole new level. In this brief article, we outlined some of the great opportunities and challenges for physiologists at this exciting time of physiological sciences, and used our own experience from the last ten years as an example to discuss how we could expand and go beyond the combination of physiology and genomics to achieve a systems understanding of biology.