Appropriate activation of B cells is required for mounting protective humoral immune responses. B‐cell activation is initiated following specific recognition of antigen by the B‐cell receptor (BCR) and results in the generation of antibody‐secreting plasma cells and long‐lived memory cells. Initial imaging approaches revealed that B cells undergo dramatic molecular and morphological reorganizations following recognition of antigen. A number of these studies pointed to a role for the underlying cytoskeleton in regulating early events of B‐cell activation. More recently, groundbreaking advances in imaging technologies have enabled direct visualization of the role for the cytoskeleton in regulating events at the B‐cell membrane. Indeed, we have demonstrated that an ezrin‐defined actin network shapes BCR diffusion and signaling both in the resting state and following antigen‐induced activation. Importantly, alongside these in vitro imaging approaches, it has been demonstrated that mutations in cytoskeleton regulators such as CD19, dedicator of cytokinesis 8 (DOCK8), and Wiskott‐Aldrich syndrome protein (WASp) are often associated with antibody deficiency syndromes in humans, establishing the importance of cytoskeleton reorganizations in conferring effective adaptive immunity.