A diverse array of successful, first-generation SARS-CoV-2 vaccines have played a huge role in efforts to bring the COVID-19 pandemic under control, even though inequitable distribution still leaves many vulnerable. Additional challenges loom for the next phase. These include optimizing the immunological rationale for boosting—how often and with what—and the best approaches for building a future-proofed, durable immune repertoire to protect against oncoming viral variants, including in children. The landscape of vaccine producers and technologies is likely to become even more heterogeneous. There is a need now for appraisal of future approaches: While some favor frequent boosting with the first-generation, ancestral spike vaccines, others propose frequent readjustment using current variant sequences, polyvalent vaccines, or pan-coronavirus strategies.