The immune system plays a central role in human health. The activities of immune cells, whether defending an organism from disease or triggering a pathological condition such as autoimmunity, are driven by the molecular machinery of cellular signaling systems. Decades of experimentation have elucidated many of the biomolecules and interactions involved in immune signaling and regulation, and recently developed technologies have led to new types of quantitative, systems-level data. To integrate such information and develop nontrivial insights into the immune system, computational modeling is needed, and it is essential for modeling methods to keep pace with experimental advances. In this chapter, we focus on the dynamic, site-specific, and context-dependent nature of interactions in immunoreceptor signaling (i.e., the biomolecular site dynamics of immunoreceptor signaling), the challenges associated with capturing these details in computational models, and how these challenges have been met through use of rule-based modeling approaches.