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Defensins and cathelicidins belong to antimicrobial peptides (AMP), called also the natural antibiotics. They are found in Prokaryotes and Eukaryotes, also are synthesized in plants. These molecules were described in bacteria, invertebrates, vertebrates, also in mammals including humans. The amino-acids sequence is determined for about 880 antimicrobial peptides, and their classification is difficult and complex. These oligo- and polypeptides, are killing the microbes or inhibit their growth, are bactericidal to Gram-negative, Gram-positive bacteria, neutralizing toxins, demonstrated antiviral activity. AMP are multifunctional molecules, playing the first line of defense in human organism as effectors of unspecific immunity, with a broad spectrum of activity against pathogens, are characterized by controlling the physiological bacterial flora, often acting synergistically, are produced in different cells as defense against mechanisms of microbial resistance. They are chemotactic to neutrophiles and T cells, activate the dendritic cells. In human organism defensins are expressed in several cells and tissues, in neutrophiles, platelets, epithelial cells, in liver, skin, eye conjunctiva. Deficiency of defensins or cathelicidins cause pathological symptoms in atopic allergies or in Kostman disease. Several synthetic peptides are currently at the final phases of clinical trials regarding treatment of various bacterial infections. Defensins or cathelicidins could be also efficient as adjuvants or carriers for vaccines, in dairy industry as preservatives. This work presents some problems concerning the occurrence of AMP, especially defensins and cathelicidins of mammals, their classification, structure, various functions and mechanisms of bactericidal activity, and also their use in treatment of some infectious diseases.