By interactions with other microbes, free-living amoebae play a significant role in microbiology, environmental biology, physiology, cellular interactions, ecology and evolution. Here, we discuss astonishing interactions of bacteria and amoebae, in the light of evolution and functional aspects impacting human health. In favourable environmental conditions, the interaction of Acanthamoeba with non-virulent bacteria results in lysis of the bacteria. However, the interaction with weak-virulent bacteria results in a symbiotic relationship or amoebal lysis may occur. The microbial survival of amoebae in harsh environments, ability to interact with bacteria, and their ability to aid transmission to susceptible hosts is of great concern to human, animal and ecosystem health.