The Oral cavity is a reservoir of bacteria with high biodiversity, however, not all species can cause invasive diseases. Identification of pathogenic bacteria in the oral lesions is challenging because cultivation of specimens from this non sterile site invariably yields a diversity of bacteria, making associations between cultivated bacteria and particular oral lesions difficult. Periodontitis is a multifactorial disease which might have a systemic or hereditary component in addition to its bacterial aetiology. It is highly prevalent worldwide, affects 30-50% of the population in developed countries, but only ~10% present with severe forms. The microbial aetiology of periodontal disease has been proved since long time ago, approximately 500 species or more have been detected in the gingival sulcus, some of them are widely regarded as major pathogens in periodontitis. Periodontal microbiota are more heterogeneous than earlier believed, in dentistry, gram-negative organisms were considered to be the predominant bacteria in periodontitis; however, gram-positive organisms found in deep, diseased sites are proposed to be the most important pathogens in periodontitis recently. Using antibiotics in controlling periodontal diseases is essential, which either suppress the growth of microorganism or destroy them. Drugs used to treat periodontal disease can be used systemically or locally, however, some periodontopathic bacteria can develop resistance to certain antimicrobials specially in refractory periodontitis and aggressive periodontitis cases.