Biological systems feature organization on length scales ranging from molecular to macroscopic, and reconfigure on time scales ranging from ultrafast to an organism’s lifespan. Connections across these disparate scales present intriguing questions and inspiring challenges for statistical mechanics. We work to address these questions and challenges in contexts including protein segregation within lipid bilayers, topological rearrangement of these membranes, assembly of protein microcompartments, and energy transfer processes of photosynthesis. Of particular interest is the mechanism by which microscopic events trigger collective response, as when reorganization of a modest number of lipid and solvent molecules promote the fusion of lipid membranes. Similarly, protein dynamics are advanced by fast microscopic motions of its side chains and solvating water molecules, but the conformational changes and supermolecular assembly mediated by these fluctuations can proceed over dramatically larger scales. To bridge this divide, we make use of atomistically detailed models and also devise coarse-grained descriptions that permit thorough investigation. Accessing the behaviors of greatest interest often requires innovating computational sampling methodology as well.