Norfloxacin-azole hybrids 3 and 6a,b were synthesized starting from norfloxacin. The treatment of these compounds with amines as a one-pot three-component reaction produced the corresponding amino derivatives 4a,b, 7a-g and 8a,b in good yields. The conventional and microwave-assisted methods were used with the latter method being more efficient. The structures of the synthesized compounds were characterized by elemental analysis, IR, H-1 NMR, C-13 NMR and MS. All compounds were screened for their antimicrobial activities. Most of them exhibit excellent antibacterial activity but are not active against selected fungi.