Rationale for fluid resuscitation is to increase mean systemic filling pressure, venous return, and cardiac output by increasing circulatory stressed volume. However, several conditions must be fulfilled to achieve desirable outcomes from fluid resuscitation. Vasopressors are also important components of resuscitation in septic shock (SS) and can potentially supplement the beneficial effects of fluid. However, the potential benefits of vasopressors must be weighed against several harms associated with vasopressors. Risks associated with vasopressors are more pronounced with underfilling of circulation and in higher doses. Current physiological and clinical evidence support intravenous fluids as the first-line resuscitation agent in SS with vasopressor infusion as a supplement to the same.