Centers for Disease Control and Prevention (CDC) and FDA each affirmed that antibiotic-resistant infections and the lack of new drugs to treat them pose a significant public health threat. Increased isolation of MRSA/MR-CoNS infections in both community and hospital setups, followed by emergence of pan-resistance (PDR) and extreme drug resistance (XDR) among Gram negative bacteria has lead to serious concerns among clinicians worldwide. Drastic decrease in the development of new antibiotics in the recent years by nearly 75% aggravates the situation. The global scientific community in search for an alternative solution found that the evaluation and use of Old Antibiotic compounds is the easiest and promising option. Low use of old antibiotic compounds has helped them to remain active against a large number of prevalent bacterial isolates. Compounds like amino glycosides, chloramphenicol, nitrofurantoin, polymixins, trimethoprime-sulphamethoxazole are re-emerging as potential means to combat infections. A total of 8,344 bacterial cultures were isolated from Feb 2013 till June 2014. MIC of colistin, vancomycin, trimethoprime-sulphamethoxazole, tetracycline, gentamicin, amikacin, tobramycin, chloramphenicol, linezolid, clindamycin and nitrofurantoin was tested against 2,314 Gram Positive and 6,030 Gram Negative isolates. MIC values prove that the old antibiotics are an excellent option to treat multi-drug resistance. In order to avoid entering the Post-Antibiotic era use of old antibiotics has to gain momentum in the years to come. The availability of novel molecular modification methods helps to reduce the toxicity and efficacy drawbacks of some of the old antibiotic compounds. More laboratory and clinical studies will lead to revival of many of the old antibiotic compounds.