Bacteria in nature are “plagued“ by various unpredictable environmental stresses, being population diversity one of the strategies adopted to survive. Phenotypic switching is one of the evolution processes that causes commutation between phenotypic states. This phenomenon shows up as variation in colony morphology. Alterations in colony morphotype traits may reveal altered cellular basis phenotype which can confer ensured virulence, antimicrobial resistance and persistence. However, the specific correlation between those traits and the biological impact is unknown. Phenotypic switching also occurs during biofilm formation, in that, bacteria have to adapt to this mode of growth expressing different phenotype traits often distinct from those expressed during planktonic growth. Often, after severe stresses, it is observed the survival of a small non-growing population, the persisters cells. The persister-state is fully reversible under growth stimulating conditions and therefore does not depend on genetic alterations. Bacterial persistence has been pointed out as switching between growing and dormant cells. Nevertheless, not only the responsive switching to environmental changes is important for survival of bacteria. Inherent heterogeneity may also be of major importance in environmental adaptation and persistence. Control of stress-response gene expression determines whether bacteria can survive to changing conditions and compete for the resources it needs to proliferate. Reversible phenotypic switching offers considerable advantages over conventional irreversible mutations. This chapter discusses the impact of generating population-level diversity on important clinical issues as resistance, virulence and persistence. It highlights that even though the growing interest and relevance of this phenomenon and its impact on bacterial ecology, the evolutionary origins and adaptive significance remain poorly understood
