Antibiotic resistance is a universal warning to human health; by 2050, it is expected that the mortality rate due to antimicrobial resistance (AMR) will exceed 10 Million. Heteroresistance (HR) is a phenomenon in which subpopulations of cells exhibit lower levels of antibiotic susceptibility compared to the main population. There are no standard methods to detect HR leading to inappropriate use of this expression. HR has been distinguished since 1947 and reported in Gram-negative and Gram-positive bacteria. Recently, HR is so prevalent in various bacterial species against the plethora of antibiotic classes. HR which has an unstable phenotypic character, having different mechanisms with non-standard methods to be determined, prevents recognition of the degree to which this phenomenon is precarious and its consequences. In 2009, World Health Organization (WHO) has defined antibiotic resistance (AbR) as a critical public health threat causing death rates more than that caused by cancer and such serious diseases. Consequently, understanding the novel and often under-recognized mechanisms of resistance that represent barriers to antibiotic efficacy is vital so as to combat resistance with new therapeutic approaches. Eventually, a fundamental issue is whether we can predict why some resistant clones have the ability to survive despite the perishing of the main population. In this review, we will assess the available literature on bacterial HR suggesting recommendations for the definition and determination criteria for antibiotic HR to help assess the treatment failure caused by heteroresistant bacteria.