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Anticoagulation is a critical component in the treatment of cardiovascular diseases. Large randomised controlled trials have demonstrated that direct oral anticoagulants (DOACs) are effective and safe for stroke prevention in patients with atrial fibrillation (AF) and treatment or prevention of venous thromboembolism. Nevertheless, for specific cardiac indications and patient characteristics, vitamin K antagonists (VKAs) rather than DOACs are either preferred, or the benefit of DOACs in comparison to VKAs remains uncertain. These include, among others, mechanical heart valves, AF associated with moderate-to-severe mitral stenosis, left ventricular or atrial thrombus, and older patients with frailty. As VKAs will continue to play a vital role in the management of patients with cardiovascular diseases in the foreseeable future, this review discusses cardiac indications and patient characteristics that necessitate the use of VKAs and general management principles of VKA therapy.