Antimicrobial resistance is one of the most significant threats to public health on a global scale, leading to a gradual decline in the effectiveness of existing antibiotics. This situation necessitates the development of more rational and multidimensional design strategies that go beyond conventional single-target antimicrobial agents. Heterocyclic compounds stand out as “privileged scaffolds” in modern antimicrobial drug design due to their structural diversity, electronic properties, and capacity for strong interaction with biological targets. This book chapter comprehensively addresses current approaches to the design of new-generation antimicrobial agents based on heterocyclic compounds, discussing synthesis, molecular design, mechanism, computational methods, and biological evaluation from a holistic perspective.

Within the scope of the chapter, the strategic roles of heterocyclic systems in antimicrobial design, primarily benzimidazole, triazole, oxadiazole, and azole derivatives, are examined, and the multi-target potential and resistance suppression advantages of hybrid pharmacophore approaches are evaluated. Furthermore, docking–experimental result discrepancies, target specificity issues, limited efficacy against biofilm formation, ADME/toxicity mismatches, and scaling challenges are analyzed in detail with literature support. Additionally, the limitations of molecular dynamics simulations and current computational.