Utilization of antibiotics as an adjunctive therapy to our therapeutic dental procedures is very common and is increasing in contemporary dental therapy. Antibiotics are not a benign therapeutic entity. With the emergence of bacterial resistance from over usage, the potential for negative drug interactions and concern regarding the level of clinical effectiveness, good stewardship in prescribing antibiotics for our dental patients is essential. Practical clinical approaches with evidence regarding therapeutic value in antibiotic usage in the management of periodontal disease. implant therapy with associated grafting for site development, endodontic infections, and combined endodontic/periodontal infections will be discussed. Antibiotic usage in treatment of dental patients relative to the updated guidelines on orthopedic joint replacements, cardiovascular concerns as well as the risk for allergic response, adverse reactions and negative drug interactions will also be reviewed.