Co-trimoxazole appropriates to category of broad-spectrum antimicrobial. They are active upon administration in vitro against an extensive collection of microorganisms. Their application in medical field has roughly spanned over decade now. There are numerous approaches that were progressed for improving their effectiveness towards their antimicrobial potency. However, routine use of this could accelerate the chance of bacterial resistance, and portrait it ineffective when required to treat infection. Consequently, newer investigations are necessary to keep the drug effective by minimise the development of resistance and maximise its safe use. Safe use is meant by safe delivery of drug in low dose, low frequency at the targeted molecule by effective ways. This can be achieved by using nanocarrier systems as they possess smart characteristics of effective drug delivery. These nanocarrier systems are including nanoparticle, liposomes, nanogels etc. Present review article deals with the historical perspectives with regards to co-trimoxazole, their mechanism of act/resistance and spectrum of activity in first section. In second portion different novel carriers, importance and application of nanogels, rational for co-trimoxazole nanogels are discussed. In conclusion, different literatures have proved the efficacy of nanogels in delivery of antimicrobial drug similar to co-trimoxazole. In the present time very less data is available for delivery of this drug with novel carriers. Therefore, this review aims to encourage researchers for creating some new findings in this perspective.