Antimicrobials are effective for eradication of pathogens but progressive increase in global trend of antimicrobial resistance (AMR) especially against last resort drugs is worrying and pose a significant threat to human health. Emergence and spread of AMR worldwide is due to reckless use of antibiotics in human, livestock, food and agriculture sector. The worldwide emergence of plasmid borne tigecycline and colistin resistance has raised significant health concerns due to ability of horizontal transfer and being last resort antibiotics. Plasmid mediated colistin resistance (mcr-1, mcr-2) has been detected in human, poultry and cattle from Pakistan mainly in isolates of A. bumannii and E. coli highlighting horizontal transfer of AMR genes, the first case of plasmid mediated tigecycline resistance tetX has also been reported in clinical isolates of E. coli from Pakistan. This emerging resistance against last resort antibiotics colistin, tigecycline, carbapenem along with jeopardizing their efficiency will also restrict the treatment options for medical workers. This situation calls for urgent attention and implementation of effective strategies to combat AMR in Pakistan.