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Heavy metal pollution is one of the most serious environmental problems, due to metal ions persistence, bioavailability, and toxicity. There are many conventional physical and chemical techniques traditionally used for environmental clean-up. Due to several drawbacks regarding these methods, the use of living organisms, or bioremediation, is becoming more prevalent. Biotechnological application of microorganisms is already successfully implemented and is in constant development, with many microbial strains successfully removing heavy metals. This paper provides an overview of the main heavy metal characteristics and describes the interactions with microorganisms. Key heavy metal resistance mechanisms in microorganisms are described, as well as the main principles and types of heavy metal bioremediation methods, with details on successful pilot scale bioreactor studies. Special attention should be given to indigenous bacteria isolated from the polluted environments since such species are already adapted to contamination and possess resistance mechanisms. Utilization of bacterial biofilms or consortia could be advantageous due to higher resistance and a combination of several metabolic pathways, and thus, the possibility to remove several heavy metals simultaneously. Novel technologies covered in this review, such as nanotechnology, genetic engineering, and metagenomics, are being introduced to the field of bioremediation in order to improve the process. To conclude, bioremediation is a potentially powerful solution for cleaning the environment.