Most of the important antibiotics that are in use today have originally come from Streptomyces bacteria. However, bioactive molecules produced by indigeneous Streptomycesfrom Nepal remain largely unexplored.Novel antibiotics with new mechanism of actions are constantly required due to the growing prevalence of resistant pathogens including methicillin-resistant Staphylococcus aureus (MRSA). The present study aimed to explore the antibiotic potentials of Streptomyces strains isolated from high altitude soil biotopes of Nepal against multidrug resistant pathogens. Streptomyces strains were initially characterized by morphological, physiological and biochemical analyses. Further identification of Streptomycesisolates was done by 16S rRNA gene sequence analysis and their taxonomic positions were confirmed by phylogenetic analyses using BLAST searches and on EzTaxon Server. Importantly, almost all isolates exhibited antibiotic activity against MRSA. In addition,most ofthese strains showed antibiotic activity against multidrug resistant Klebsiella pneumoniae, Bacillus subtilis and Micrococcus luteus.