Group A streptococcal (Streptococcus pyogenes) diseases remain a major public health problem in developing countries as well as in the indigenous populations of developed countries. In view of the large number of Group A streptococcal infections and the potential for sequelae such as rheumatic heart disease, control strategies including the development of an anti-streptococcal vaccine that is able to prevent infection and colonization is important. In this article, we discuss the epidemiology and strain variability of Group A streptococcus and how this is rendering vaccine development more challenging. We discuss vaccine strategies with a focus on the conserved region of the M protein and present a viewpoint for the impediments and the way forward.