Hemodynamic stabilization and preservation of organ perfusion are central elements in the management of septic shock. This is achieved by fluid resuscitation and by administration of vasoactive agents. Current guidelines recommend norepinephrine as the first-line vasoactive substance. In cases of high norepinephrine requirements the addition of nonadrenergic vasopressors is recommended. Furthermore, evidence suggests that early use of complementary vasoactive substances may provide additional benefits. Such a regimen, in terms of a broad-spectrum vasopressor approach, appears physiologically plausible. Post hoc analyses of studies investigating vasopressin or angiotensin II also suggest that specific subphenotypes may particularly benefit from individual vasoactive agents. Adjunctive therapy with hydrocortisone and fludrocortisone can improve vasopressor responsiveness and reduce mortality. In cases of cardiac dysfunction, a trial with dobutamine or a switch from norepinephrine to epinephrine is recommended. To enhance inodilator effects, milrinone or levosimendan may represent additional therapeutic options for certain patients. Although short-acting beta-blockers are not part of the standard treatment for septic shock, they may, in selected cases, contribute to hemodynamic improvement in patients with inadequately high sinus tachycardia or atrial tachyarrhythmias. Based on pathophysiological considerations and the currently available evidence, targeted use of specific vasoactive substances in defined subphenotypes may be justified. An initial broad-spectrum vasopressor strategy incorporating biomarkers such as renin and patient-specific characteristics followed by a focused de-escalation approach could represent a promising concept. However, the effectiveness of these strategies requires further investigation in randomized controlled trials.