The discovery and production of (synthetic) antibiotics in the first half of the previous century has been one of medicine’s greatest achievements. The use of antimicrobial agents has reduced morbidity and mortality of humans and contributed substantially to human’s increased life span. The issue of antibiotic resistance has received considerable attention due to the problem of the emergence and rapid expansion of antibiotic-resistant pathogenic bacteria. Antibiotic resistance exhibited by bacteria can be intrinsic, acquired, or adaptive. Therefore, efforts to develop antibiotics and study mechanisms of resistance should be continuous, resilient and steady. In the following sections, we will focus on the molecular and biochemical mechanisms of bacterial resistance, illustrating specific situations that are often encountered in clinical practice.