The search for antimalarial compounds continues to be an area of intensive investigation in medicinal chemistry. This review presents the structural variations around the indolone-N-oxide core. From these pharmacomodulation studies, new antiplasmodial agents with various structures have emerged. Most of the molecules generated from reduced forms of the indolone scaffold have led to compounds with antiplasmodial properties. These results confirm the importance of the redox reversibility of the bioreducible N=C bond in these series to obtain antimalarial activities.