To persist in the oral cavity, bacteria must be able to tolerate rapid and substantial environmental fluctuations, particularly in pH and nutrient source and availability. Various species of Streptococcus, one of the most abundant genera in the mouth, are associated with oral health, as well as with dental caries. Cariogenic streptococci depend on a biofilm lifestyle for survival and persistence in the oral cavity and have developed sophisticated mechanisms to cope with environmental stresses. Here, we analyze the primary factors that allow these bacteria to emerge as significant members of tooth biofilms during adverse conditions. Our focus is on the molecular mechanisms of biofilm formation, stress tolerance and sugar metabolism by pathogenic oral streptococci, mainly Streptococcus mutans. Overlaps in the roles and regulation of these virulence attributes are highlighted and areas of research that deserve further investigation are proposed.