Background:Drug-resistant isolates remain an important hospital-acquired bacterial pathogen, add significantly to hospital stays and especially problematic in high-impact medical areas such as intensive care units. Klebsiella pneumoniae is the most common cause of nosocomial respiratory tract, and the second-most frequent cause of Gram-negative bacteraemia and urinary tract infections. It is essential to detect the beta lactam resistance in K. pneumoniae for proper antibiotic therapy and to limit the spread the infection. Objectives: The study was designed to review the rates of extended-spectrum β-lactamases (ESBL), metallo beta lactamases (MBL) and Ampicillin resistance gene group C (AmpC) beta lactamases production among K. pneumoniae isolates and to assess the best phenotypic method for detection of the resistance. Methodology: This study included 200 isolates obtained from patients admitted to different Departments in Assiut University Hospital. Screening and phenotypic confirmatory tests for resistance were done. Results: The Percentages of B –Lactamase enzymes producers from 50 isolates of K. pneumoniae were11 (22%) isolates not resistant; 6 (12%) by screening with antibiotic sensitivity tests and 5(10%) by the gold standard phenotypic tests. The remaining 39of 50 isolates (78%) were resistant and distributed as follow; Ten strains (20%) were ESBL alone, 2 (4%) were ESBL and AmpC, 4(8%) were ESBL and Carbapenemases, 13(26%) were AmpC producers alone and 10 (20%) were Carbapenemases producers alone. The combined disk test showed high sensitivity and specificity for detection of ESBL and MBL, For AmpC detection; the disk approximation test showed higher sensitivity and specificity than boronic acid. Conclusion: The rate of Beta lactamases production by K.pneumoniae is seriously increased, the most common type of beta lactamases in K.pneumoniae was the ESBL32% then AmpC30 %and lastly the Metallo beta lactamase (MBL) 28%. The phenotypic confirmatory tests showed high sensitivity and specificity and proved to be reliable methods for detection ofthe beta lactamase resistance, genotypic tests are recommended to be a gold standard tests to increase the specificity of the phenotypic tests.