Owning the merits of low-cost, unique electronic and geometric properties, atomically dispersed M-N-C materials have been extensively examined as robust electrocatalysts for many important electrochemical reactions. Nevertheless, it remains a grand synthetic challenge to fabricate such materials with a high concentration of isolated metal active sites, as the formation of metal clusters/nanoparticles seems to be inevitable during the calcination process due to the high surface free energy of single-atom metals. As a result, although M-N-Cs have been successfully tuned to display remarkable activities per metal atomic site, their overall catalytic performances are still unsatisfactory. In this current opinion article, we summarize recent advances in innovative strategies to increase the active-site density of M-N-Cs and also propose the future opportunities and challenges for fostering the practical application of M-N-Cs in electrochemical devices.