Research in systems biology requires the collaboration of researchers from diverse backgrounds, including biology, computer science, mathematics, statistics, physics, and biochemistry. These collaborations, necessary because of the enormous breadth of background needed for research in this field, can be hindered by differing understandings of the limitations and applicability of techniques and concerns from different disciplines. This comprehensive introduction and overview of system modeling in biology makes the relevant background material from all pertinent fields accessible to researchers with different backgrounds.