The rapid increase in drug-resistant infections has highlighted the need for alternative antimicrobial therapies. Antimicrobial peptides (AMPs) are a growing class of natural and synthetic peptides with a wide spectrum of targets, including viruses, bacteria, fungi, and parasites. This review covers the history and recent developments of AMPs, their major types, modes of action, and mechanisms of resistance. AMPs are classified into antiviral, antibacterial, antifungal, and antiparasitic peptides, each with distinct mechanisms of action. AMPs can disrupt cell membranes, inhibit intracellular processes, or target specific intracellular targets. Designing new synthetic AMPs involves considering physicochemical properties such as length, charge, helicity, hydrophobicity, amphipathicity, and solubility. Post-translational modifications and computer-assisted methods are also used to enhance AMP activity and specificity. AMPs show promise in controlling biofilms and persister cells, which are highly tolerant to antibiotics. However, resistance mechanisms, including constitutive and inducible resistance, pose challenges. Despite these challenges, the lipid bilayer structure of bacterial membranes makes it difficult for bacteria to develop complete resistance to AMPs. The future of AMP research holds potential for developing new antimicrobial agents to combat drug-resistant infections.The rapid increase in drug-resistant infections has highlighted the need for alternative antimicrobial therapies. Antimicrobial peptides (AMPs) are a growing class of natural and synthetic peptides with a wide spectrum of targets, including viruses, bacteria, fungi, and parasites. This review covers the history and recent developments of AMPs, their major types, modes of action, and mechanisms of resistance. AMPs are classified into antiviral, antibacterial, antifungal, and antiparasitic peptides, each with distinct mechanisms of action. AMPs can disrupt cell membranes, inhibit intracellular processes, or target specific intracellular targets. Designing new synthetic AMPs involves considering physicochemical properties such as length, charge, helicity, hydrophobicity, amphipathicity, and solubility. Post-translational modifications and computer-assisted methods are also used to enhance AMP activity and specificity. AMPs show promise in controlling biofilms and persister cells, which are highly tolerant to antibiotics. However, resistance mechanisms, including constitutive and inducible resistance, pose challenges. Despite these challenges, the lipid bilayer structure of bacterial membranes makes it difficult for bacteria to develop complete resistance to AMPs. The future of AMP research holds potential for developing new antimicrobial agents to combat drug-resistant infections.