The interest in developing antimicrobial surfaces is currently surging with the rise in global infectious disease events. Radiation-induced graft copolymerization (RIGC) is a powerful technique enabling permanent tunable and desired surface modifications imparting antimicrobial properties to polymer substrates to prevent disease transmission and provide safer biomaterials and healthcare products. This review aims to provide a broader perspective of the progress taking place in strategies for designing various antimicrobial polymeric surfaces using RIGC methods and their applications in medical devices, healthcare, textile, tissue engineering and food packing. Particularly, the use of UV, plasma, electron beam (EB) and γ-rays for biocides covalent immobilization to various polymers surfaces including nonwoven fabrics, films, nanofibers, nanocomposites, catheters, sutures, wound dressing patches and contact lenses is reviewed. The different strategies to enhance the grafted antimicrobial properties are discussed with an emphasis on the emerging approach of in-situ formation of metal nanoparticles (NPs) in radiation grafted substrates. The current applications of the polymers with antimicrobial surfaces are discussed together with their future research directions. It is expected that this review would attract attention of researchers and scientists to realize the merits of RIGC in developing timely, necessary antimicrobial materials to mitigate the fast-growing microbial activities and promote hygienic lifestyles.