An effective malaria vaccine that reduces morbidity and mortality and contributes to malaria elimination is a much-needed tool, particularly in endemic areas where health-care delivery and vector control efforts are difficult to sustain. RTS,S/AS01 is likely to be the first licensed malaria vaccine and represents an important step toward malaria control and elimination. However, a partially effective vaccine such as RTS,S/AS01 poses challenges for evaluating the efficacy of second-generation malaria vaccines. Whole-sporozoite immunization approaches have shown promising results, inducing sterile immunity in small-scale trials of malaria-naïve adults, but may not achieve durable sterile protection in endemic populations. Vaccines targeting both the pre-erythrocytic and the erythrocyte-invasive form of the parasite (merozoites) may abrogate breakthrough infections by neutralizing merozoites emerging from infected hepatocytes, whereas vaccines targeting the sexual stages seek to break the transmission cycle. Moving forward, a multi-stage vaccine could be the next step toward malaria elimination and eradication.