The remarkable increase in resistance to currently available antibiotics to Gram-negative pathogens particularly multidrug resistant (MDR) Pseudomonas aeruginosa and Acinetobacter baumannii, This has resulted in increasing use of older under evaluated antibiotics such as fosfomycin, nitrofurantoin,  and Trimethoprime-Sulfamethoxazole for the treatment of infections caused by MDR pathogens. However, limited in-vitro pharmacodynamic data for fosfomycin and nitrofurantoin against Pseudomonas Spp., and Acinetobacter Spp., is available in literature. The current study demonstrates in-vitro activities of fosfomycin and nitrofurantoin against Pseudomonas and Acinetobacter pathogens (425 Pseudomonas Spp., and 352 Acinetobacter Spp., Total: 777 Strains), isolated from Indian tertiary care hospitals.  The minimum inhibitory concentration (MIC50/90) of fosfomycin and nitrofurantoin along with comparator antibiotics were determined using Clinical and Laboratory Standards Institute recommended agar dilution method. Fosfomycin demonstrated excellent in-vitro activity against Pseudomonas while in nitrofurantoin demonstrated poor activity against Pseudomonas Spp.,. Fosfomycin and nitrofurantoin did not show promising activities against Acinetobacter Spp.,. By applying E. coli breakpoints, the susceptibility rates of fosfomycin for Pseudomonas Spp., and Acinetobacter Spp., were 72.4%, and 14.8%, respectively. By applying respective breakpoints, the susceptibility rates of comparator drugs, including imipenem and meropenem, were lower than fosfomycin. Susceptibility rate of nitrofurantoin for Pseudomonas Spp., and Acinetobacter Spp., was <1.2% suggesting its poor activity. The susceptibility rate of fosfomycin was > 70% for Pseudomonas isolates, including strains expressing carbapenemases is encouraging finding and supports its potential use. Nitrofurantoin did not show activity against both the Spp., with susceptibility rates <1.2%. Keywords: Fosfomycin, Nitrofurantoin Gram-negative, Multi Drug Resistant, A. baumannii and P. aeruginosa.