As one of the most common oral diseases in kids, early childhood caries affects the health of children throughout the world. Clinical investigations show the copresence ofCandida albicansandStreptococcus mutansin ECC lesions, and mechanistic studies reveal co-existence ofC. albicansandS. mutansaffects both of their cariogenicity. Clearly a comprehensive understanding of the interkingdom interaction between these two microorganisms has important implications for ECC treatment and prevention. To this end, this review summarizes advances in our understanding of the virulence of bothC. albicansandS. mutans. More importantly, the synergistic and antagonistic interactions between these two microbes are discussed.