Germinal center (GC) B cells are the source of the high-affinity, class-switched antibodies required for protective immunity. The unique biology of GC B cells involves iterative rounds of antibody gene somatic hypermutation coupled to multiple selection and differentiation pathways. Recent advances in areas such as single cell and gene editing technologies have shed new light upon these complex and dynamic processes. We review these findings here and integrate them into the current understanding of GC B cell replication and death, the retention of high-affinity and class-switched B cells in the GC, and differentiation into plasma and memory cell effectors. We also discuss how the biology of GC responses relates to vaccine effectiveness and outline current and future challenges in the field.