Vancomycin is used to manage methicillin-resistant Staphylococcus aureus (MRSA) and other bacterial infections that are Gram-positive in nature. Linezolid belongs to the oxazolidinone class of antibiotics, which is primarily used to treat vancomycin-resistant Enterococcus (VRE), MRSA, diabetic foot, soft tissue, and skin infections. Here, we discuss vancomycin and linezolid dosing in obese patients, their mechanism of actions, pharmacokinetics, problems with dosing and evaluation of several dosing protocols in the obese patient population. There is no generally accepted dosing protocol for linezolid and vancomycin. Evidence suggests that using trough concentrations alone is insufficient for estimating vancomycin and linezolid exposure accurately as many researchers have revised protocol guidelines, developed more rigorous dosing and monitoring guidelines, or developed novel dosage strategies to meet the needs of overweight patients. Peaks and troughs measurement should be considered because it improves precision and reduces the area under the curve (AUC) estimate bias. To provide better dosing guidelines in this vulnerable group, obese patients must be included in all phases of drug design.