Pseudomonas aeruginosa is known for its antibiotic resistance to the clinicians. The infections caused by this pathogen are hard to treat because of its highly versatile property to mutate and acquire drug resistance. Pseudomonas aeruginosa also possesses intrinsic property of resistance to certain antibiotics like tetracyclines. However; in a practice to overcome the problem of multi drug resistance, clinicians restored the use of some antibiotics that were previously been used to treat the Pseudomonal infections; but they were discontinued because of its toxic effects. Colistin is an example of one such antibiotic. Use of Colistin was barred for its neurotoxicity. However in recent clinical trials, Colistin was reintroduced to fight with this superbug. Sadly in recent years, Pseudomonas aeruginosa developed resistance to Colistin as well. Therefore combined therapy is an alternate and suitable treatment to overcome the infections caused by multidrug-resistant Pseudomonas aeruginosa. The present study is an in vitro study; in which we tested synergy between two antibiotics namely streptomycin and Colistin on 29 clinical isolates of P. aeruginosa collected from hospitals in Jazan city KSA. The combination of two drugs showed synergistic activity on 55.1% of tested strains, while 20.6% strains had partial synergy, whereas indifferent synergy was observed in 13.8% strains and the 6.8% of strains had additive synergy. In addition to this, the drugs when combined also showed antagonism on one strain (3.44%). The present study showed synergistic action on Colistin-resistant Pseudomonas aeruginosa to greater extent (55.1%) by the two tested drugs. Hence Colistin and streptomycin can be used as a suitable combination therapy (in vivo) to treat multidrug resistant P. aeruginosa infections.